TABLE 2.
Predicted pathogenic variants in SLC19A3
| Genomic coordinate (GRCh37/hg19) | cDNA (NM_025243.3) | Protein (NP_079519.1) | dbSNP ID | Type of mutation | Polyphen-2 | SIFT | CADD Phred | Allele number | Allele count | Allele frequency (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| chr2:228566999 | c.36G>C | p.Trp12Cys | – | Missense | Probably damaging | Deleterious | 32 | 121308 | 1 | 0.0008243 |
| chr2:228566979 | C.56T>C | p.Leu19Pro | rs142553867 | Missense | Probably damaging | Deleterious | 27.9 | 121356 | 2 | 0.001648 |
| chr2:228566967 | c.68G>A | p.Gly23Asp | rs121917882 | Missense | Probably damaging | Deleterious | 26.9 | 121372 | 1 | 0.0008239 |
| chr2:228566935 | c.100T>G | p.Phe34Val | rs201603239 | Missense | Probably damaging | Deleterious | 29.8 | 121370 | 3 | 0.002472 |
| chr2:228566923 | c.112T>C | p.Tyr38His | rs368305641 | Missense | Possibly damaging | Deleterious | 25.9 | 121356 | 2 | 0.001648 |
| chr2:228566922 | c.113A>G | p.Tyr38Cys | – | Missense | Probably damaging | Deleterious | 25 | 121358 | 1 | 0.000824 |
| chr2:228566883 | c.150 + 2T>C | – | – | Canonical splice | – | – | 23.3 | 121304 | 1 | 0.0008244 |
| chr2:228564282 | c.151–2A>T | – | – | Canonical splice | – | – | 23.2 | 120730 | 1 | 0.0008283 |
| chr2:228564259 | c.172G>T | p.Val58Phe | rs200412423 | Missense | Probably damaging | Deleterious | 23.8 | 121114 | 1 | 0.0008257 |
| chr2:228564244 | c.187T>C | p.Tyr63His | rs144817990 | Missense | Probably damaging | Deleterious | 24.3 | 121286 | 14 | 0.01154 |
| chr2:228564225 | c.206C>T | p.Pro69Leu | – | Missense | Probably damaging | Deleterious | 25.6 | 121356 | 1 | 0.000824 |
| chr2:228564223 | c.208G>C | p.Val70Leu | – | Missense | Probably damaging | Deleterious | 25.7 | 121356 | 2 | 0.001648 |
| chr2:228564216 | c.215T>C | p.Val72Ala | – | Missense | Possibly damaging | Deleterious | 25.4 | 121382 | 1 | 0.0008238 |
| chr2:228564214 | c.217C>T | p.Leu73Phe | rs373943165 | Missense | Possibly damaging | Deleterious | 25.2 | 121384 | 2 | 0.001648 |
| chr2:228564189 | c.242C>T | p.Pro81Leu | – | Missense | Probably damaging | Deleterious | 27.5 | 121402 | 2 | 0.001647 |
| chr2:228564177 | C.254T>C | p.Leu85Ser | – | Missense | Possibly damaging | Deleterious | 22.7 | 121404 | 1 | 0.0008237 |
| chr2:228564126 | c.305G>A | p.Gly102Glu | – | Missense | Probably damaging | Deleterious | 31 | 121412 | 1 | 0.0008236 |
| chr2:228564112 | c.319C>A | p.Gln107Lys | – | Missense | Probably damaging | Deleterious | 27.7 | 121410 | 1 | 0.0008237 |
| chr2:228564098 | c.333C>A | p.Phe111Leu | – | Missense | Probably damaging | Deleterious | 26.5 | 121398 | 1 | 0.0008237 |
| chr2:228564087 | C.344T>C | p.Met115Thr | – | Missense | Possibly damaging | Deleterious | 23.5 | 121394 | 1 | 0.0008238 |
| chr2:228564085 | c.346G>A | p.Val116Ile | – | Missense | Possibly damaging | Deleterious | 25.2 | 121388 | 1 | 0.0008238 |
| chr2:228564082 | c.349A>G | p.Thr117Ala | – | Missense | Possibly damaging | Deleterious | 23.2 | 121370 | 1 | 0.0008239 |
| chr2:228564058 | c.373G>C | p.Ala125Pro | – | Missense | Probably damaging | Deleterious | 29.8 | 121342 | 5 | 0.004121 |
| chr2:228564054 | c.377A>C | p.Tyr126Ser | – | Missense | Probably damaging | Deleterious | 28.5 | 121334 | 1 | 0.0008242 |
| chr2:228564050 | c.381A>G | p.Ilel27Met | – | Missense | Probably damaging | Deleterious | 20.1 | 121330 | 1 | 0.0008242 |
| chr2:228564048 | c.383A>G | p.Tyr128Cys | – | Missense | Probably damaging | Deleterious | 26 | 121330 | 15 | 0.01236 |
| chr2:228564021 | c.410A>C | p.Gln137Pro | – | Missense | Probably damaging | Deleterious | 25.9 | 121288 | 2 | 0.001649 |
| chr2:228564021 | c.410dup | p.Arg138GlufsTer87 | – | Frameshift | – | – | 33 | 121272 | 2 | 0.001649 |
| chr2:228564021 | c.410A>G | p.Gln137Arg | – | Missense | Possibly damaging | Tolerated | 23 | 121288 | 1 | 0.0008246 |
| chr2:228564019 | c.412A>G | p.Arg138Gly | rs201318094 | Missense | Possibly damaging | Deleterious | 24.9 | 121268 | 1 | 0.0008246 |
| chr2:228564006 | c.425A>G | p.Tyr142Cys | – | Missense | Possibly damaging | Deleterious | 25.1 | 121226 | 1 | 0.0008249 |
| chr2:228563965 | c.466G>A | p.Val156Met | – | Missense | Probably damaging | Deleterious | 25.3 | 121336 | 1 | 0.0008242 |
| chr2:228563949 | C.482T>C | p.Leu161Ser | – | Missense | Probably damaging | Deleterious | 24.4 | 121352 | 1 | 0.000824 |
| chr2:228563928 | c.503C>G | p.Ser168Trp | rs139611208 | Missense | Probably damaging | Deleterious | 24.2 | 121382 | 1 | 0.0008238 |
| chr2:228563911 | c.520G>T | p.Val174Phe | rs59736804 | Missense | Possibly damaging | Deleterious | 26.4 | 121396 | 1 | 0.0008238 |
| chr2:228563889 | c.542C>T | p.Ser181Phe | – | Missense | Possibly damaging | Deleterious | 21.8 | 121404 | 1 | 0.0008237 |
| chr2:228563839 | c.592T>C | p.Phe198Leu | rs370725962 | Missense | Probably damaging | Deleterious | 29.2 | 121332 | 1 | 0.0008242 |
| chr2:228563838 | c.593T>C | p.Phe198Ser | – | Missense | Probably damaging | Deleterious | 28.6 | 121334 | 1 | 0.0008242 |
| chr2:228563832 | c.599A>G | p.His200Arg | – | Missense | Probably damaging | Deleterious | 24.5 | 121316 | 1 | 0.0008243 |
| chr2:228563646 | c.785T>C | p.Phe262Ser | – | Missense | Possibly damaging | Deleterious | 25 | 121402 | 4 | 0.003295 |
| chr2:228563614 | c.817T>G | p.Tyr273Asp | – | Missense | Probably damaging | Deleterious | 29.3 | 121404 | 1 | 0.0008237 |
| chr2:228563577 | c.854G>A | p.Trp285Ter | rs373198092 | Stop-gain | – | – | 40 | 121404 | 1 | 0.0008237 |
| chr2:228563538 | c.893A>G | p.Tyr298Cys | rs370104837 | Missense | Possibly damaging | Deleterious | 25.7 | 121326 | 2 | 0.001648 |
| chr2:228563515 | c.916A>T | p.Lys306Ter | – | Stop-gain | – | – | 37 | 121028 | 1 | 0.0008263 |
| chr2:228563476 | c.955G>A | p.Val319Ile | rs372511010 | Missense | Probably damaging | Deleterious | 34 | 119876 | 2 | 0.001668 |
| chr2:228560774 | c.1003G>C | p.Gly335Arg | – | Missense | Probably damaging | Deleterious | 34 | 121348 | 1 | 0.0008241 |
| chr2:228560744 | c.1033G>A | p.Gly345Arg | – | Missense | Probably damaging | Deleterious | 35 | 121392 | 2 | 0.001648 |
| chr2:228560725 | c.1052T>A | p.Val351Asp | – | Missense | Possibly damaging | Deleterious | 24.4 | 121402 | 1 | 0.0008237 |
| chr2:228560723 | c.1054T>G | p.Phe352Val | – | Missense | Possibly damaging | Deleterious | 25 | 121402 | 1 | 0.0008237 |
| chr2:228560707 | c.1070C>T | p.Ala357Val | – | Missense | Possibly damaging | Deleterious | 25.8 | 121398 | 7 | 0.005766 |
| chr2:228560689 | c.1088T>C | p.Met363Thr | – | Missense | Probably damaging | Deleterious | 26.4 | 121402 | 2 | 0.001647 |
| chr2:228560662 | c.1115G>A | p.Cys372Tyr | – | Missense | Probably damaging | Deleterious | 32 | 121390 | 3 | 0.002471 |
| chr2:228560623 | c.1154T>C | p.Leu385Pro | rs563607795 | Missense | Probably damaging | Deleterious | 33 | 121338 | 1 | 0.0008241 |
| chr2:228560615 | c.1162A>T | p.Thr388Ser | – | Missense | Probably damaging | Deleterious | 29 | 121322 | 1 | 0.0008243 |
| chr2:228560611 | c.1166T>C | p.Ile389Thr | rs149282475 | Missense | Possibly damaging | Deleterious | 29.6 | 121308 | 1 | 0.0008243 |
| chr2:228553024 | c.1173–1G>A | – | rs531876613 | Canonical splice | – | – | 26.3 | 119782 | 1 | 0.0008248 |
| chr2:228553013 | c.1183G>T | p.Ala395Ser | – | Missense | Probably damaging | Deleterious | 34 | 120494 | 1 | 0.0008299 |
| chr2:228553012 | c.1184C>T | p.Ala395Val | – | Missense | Possibly damaging | Deleterious | 34 | 120506 | 1 | 0.0008298 |
| chr2:228552992 | c.1204C>T | p.Arg402Cys | rs150523975 | Missense | Possibly damaging | Deleterious | 31 | 120836 | 11 | 0.009103 |
| chr2:228552992 | c.1204C>G | p.Arg402Gly | rs150523975 | Missense | Probably damaging | Deleterious | 34 | 120836 | 1 | 0.0008276 |
| chr2:228552991 | c.1205G>A | p.Arg402His | – | Missense | Possibly damaging | Deleterious | 34 | 120852 | 3 | 0.002482 |
| chr2:228552981 | c.1215G>T | p.Leu405Phe | – | Missense | Possibly damaging | Deleterious | 27.6 | 120918 | 1 | 0.000827 |
| chr2:228552961 | c.1235T>C | p.Phe412Ser | – | Missense | Probably damaging | Deleterious | 31 | 121022 | 1 | 0.0008263 |
| chr2:228552944 | c.1252C>G | p.Gln418Glu | rs368364131 | Missense | Probably damaging | Deleterious | 27.8 | 121048 | 83 | 0.06857 |
| chr2:228552934 | c.1262T>G | p.Met421Arg | – | Missense | Possibly damaging | Deleterious | 24.8 | 121042 | 1 | 0.0008262 |
| chr2:228552931 | c.1265C>T | p.Thr422Ile | – | Missense | Probably damaging | Deleterious | 28.5 | 121046 | 1 | 0.0008261 |
| chr2:228552920 | c.1276G>A | p.Val426Ile | – | Missense | Possibly damaging | Deleterious | 27.4 | 120990 | 3 | 0.00248 |
| chr2:228552905 | c.1291C>T | p.Leu431Phe | – | Missense | Probably damaging | Deleterious | 28.6 | 120926 | 1 | 0.000827 |
| chr2:228552881 | c.1314 + 1G>A | – | rs141957107 | Canonical splice | – | – | 25.8 | 120800 | 1 | 0.0008278 |
| chr2:228552279 | c.1325A>T | p.Tyr442Phe | – | Missense | Probably damaging | Deleterious | 32 | 120246 | 3 | 0.002495 |
| chr2:228552255 | c.1349C>T | p.Ala450Val | – | Missense | Possibly damaging | Deleterious | 33 | 121132 | 1 | 0.0008255 |
| chr2:228552255 | c.1349C>G | p.Ala450Gly | – | Missense | Possibly damaging | Deleterious | 29.5 | 121132 | 3 | 0.002477 |
| chr2:228552249 | c.1355T>C | p.Ile452Thr | rs140706520 | Missense | Possibly damaging | Deleterious | 26.8 | 121202 | 4 | 0.0033 |
| chr2:228552248 | c.1356delA | p.Ile452PhefsTer3 | rs140706520 | Frameshift | – | – | 34 | 121202 | 1 | 0.0008251 |
| chr2:228552233 | c.1371C>A | p.Ser457Arg | rs200054205 | Missense | Possibly damaging | Deleterious | 24.4 | 121328 | 3 | 0.002473 |
| chr2:228552129 | c.1475dup | p.Met492AsnfsTer27 | rs192876801 | Frameshift | – | – | 23.8 | 121118 | 1 | 0.0008256 |