Table 2.
In silico predictions for PPFIA3 variants
| Individuals | 1 and 2 | 3 | 4 | 5 and 6 | 7 | 8 and 9 | 10 | 11 |
|---|---|---|---|---|---|---|---|---|
| Human reference genome | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) |
| PPFIA3 variant cDNA (GenBank: NM_003660.4) | c.115C>T | c.118G>A | c.239A>C | c.240+1G>A | c.943G>T | c.1243C>T | c.1285C>T | c.1492C>T |
| PPFIA3 variant protein (GenBank: NP_003651.1) | p.Arg39Cys | p.Glu40Lys | p.Gln80Pro | N/A | p.Ala315Ser | p.Arg415Trp | p.Arg429Trp | p.Arg498Trp |
| REVEL (v.1) | 0.316 | 0.271 | 0.338 | N/A | 0.218 | 0.21 | 0.295 | 0.273 |
| CADD (v.1.6) | 31 | 30 | 26.8 | 34 | 24 | 33 | 29.2 | 25.9 |
| GERP | 4.19 | 4.19 | 4.34 | 4.34 | 4.29 | 2.12 | 2.95 | 1.41 |
| M-CAP (v.1.4) | possibly pathogenic | possibly pathogenic | possibly pathogenic | N/A | possibly pathogenic | likely benign | possibly pathogenic | possibly pathogenic |
| PolyPhen2 HumDiv | probably damaging | probably damaging | benign | N/A | benign | probably damaging | probably damaging | probably damaging |
| PolyPhen2 HumVar | probably damaging | probably damaging | benign | N/A | benign | probably damaging | probably damaging | probably damaging |
| Phylop Vertebrate | 0.945 | 9.447 | 9.02 | N/A | 9.4308 | 0.0498 | 2.25 | 2.58 |
| SIFT | damaging | damaging | damaging | N/A | damaging | damaging | damaging | damaging |
| Individuals | 12 | 13 | 14 and 15 | 16 | 17 | 18 | 19 | 20 | 20 |
|---|---|---|---|---|---|---|---|---|---|
| Human reference genome | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh37 (hg19) | GRCh38 (hg38) | GRCh37 (hg19) | GRCh37 (hg19) |
| PPFIA3 variant cDNA (GenBank: NM_003660.4) | c.1638G>T | c.2350C>T | c.2609T>A | c.2706dup | c.2717C>T | c.3307del | deletion exons 22–30a | c.2377C>A | c.2276A>G |
| PPFIA3 variant protein (GenBank: NP_003651.1) | p.Trp546Cys | p.Arg784Trp | p.Ile870Asn | p.Ser903Leu fs∗86 | p.Ser906Leu | p.Glu1103Asnfs∗8 | N/A | p.Pro793Thr | p.Lys759Arg |
| REVEL (v.1) | 0.186 | 0.158 | 0.41 | N/A | 0.207 | N/A | N/A | 0.092 | 0.183 |
| CADD (v.1.6) | 25.6 | 26.5 | 31 | N/A | 29.3 | 54 | 49 | 22.6 | 26.8 |
| GERP | 3.87 | 3.63 | 4.45 | 4.45 | 3.31 | 4.29 | N/A | 4.91 | 4.17 |
| M-CAP (v.1.4) | possibly pathogenic | possibly pathogenic | possibly pathogenic | N/A | likely benign | N/A | N/A | possibly pathogenic | possibly pathogenic |
| PolyPhen2 HumDiv | probably damaging | probably damaging | probably damaging | N/A | tolerated | N/A | N/A | probably damaging | probably damaging |
| PolyPhen2 HumVar | probably damaging | benign | probably damaging | N/A | probably damaging | N/A | N/A | probably damaging | probably damaging |
| Phylop Vertebrate | 4 | 1.609 | 7.855 | N/A | 5.756 | N/A | N/A | 3.7 | 9.17 |
| SIFT | tolerated | damaging | damaging | N/A | damaging | N/A | N/A | damaging | damaging |
Abbreviations: combined annotation-dependent depletion (CADD); genomic evolutionary rate profiling (GERP); Mendelian clinically applicable pathogenicity (M-CAP); polymorphism phenotyping v2 (PolyPhen2); sorting intolerant from tolerant (SIFT); not applicable (N/A)ano further information is available for the breakpoints for deletion in Individual 19.