Table 2. Summary of rare, possibly deleterious variants located in shared regions on chromosome X.
| Index case | Position (Hg19) | Gene | NM_number | Nucleotide change | Amino-acid change | Mutation type | rs number (dbSNP135) | rsMAF(dbSNP 135/Exome variant server) (%) | Grantham distance | SIFT | PolyPhen2 | Mutpred | SNPs&GO | Controls | Variant found in healthy man in the family | Causative status |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Family 1 | 3228257 | MXRA5 | NM_015419 | c.7987G >T | p.Gly2663Trp | Missense | rs143264543 | 0/0.02 | 184 | deleterious | damaging | 0.575 | neutral | 0/93 | NA | possible |
| 16860727 | TXLNG | NM_018360 | c.*838A >G | 3'UTR | rs140169598 | 0/- | NA | unknown | ||||||||
| 18910664 | PHKA2 | NM_000292 | c.*939T >C | 3'UTR | rs142176794 | 0/- | NA | unknown | ||||||||
| 19037757 | GPR64 | NM_001079858 | c.670C >T | p.Pro224Ser | Missense | rs140334931 | 0/0.34 | 74 | tolerated | damaging | 0.268 | neutral | NA | possible | ||
| 23801307 | SAT1 | NM_002970 | c.-162G >A | 5'UTR | rs113458958 | 0.8/- | NA | unknown | ||||||||
| 118250487 | KIAA1210 | NM_020721 | c.622G >T | p.Val208Phe | Missense | — | -/0.18 | 50 | deleterious | damaging | 0.174 | unknown | NA | possible | ||
| 124028159 | ODZ1 | NM_001163278 | c.521C >A | p.Ala174Asp | Missense | rs139486546 | 0/0.1 | 126 | deleterious | benign | 0.396 | neutral | 0/159 | NA | possible | |
| 148081861 | AFF2 | NM_002025 | c.*8999G >C | 3'UTR | rs142697456 | 0/- | NA | unknown | ||||||||
| Family 2 | 17750042 | NHS | NM_198270 | c.4351G >C | p.Ala1451Pro | Missense | — | -/- | 27 | tolerated | damaging | 0.345 | neutral | 0/88 | NA | possible |
| 130411844 | IGSF1 | NM_001170961 | c.2321A >G | p.Glu774Gly | Missense | — | -/- | 98 | deleterious | damaging | 0.484 | unknown | 0/96 | NA | possible | |
| 151092546 | MAGEA4 | NM_001011548 | c.410T >A | p.Leu137Gln | Missense | — | -/- | 113 | deleterious | damaging | 0.827 | disease | 0/96 | NA | possible | |
| 153734897 | FAM3A | NM_021806 | c.*245A >G | 3'UTR | rs145895727 | 0/- | NA | unknown | ||||||||
| Family 4 | 3240238 | MXRA5 | NM_015419 | c.3488G >A | p.Arg1163His | Missense | rs139106444 | 0/0.36 | 29 | deleterious | damaging | 0.399 | neutral | 1/130 male | yes (grand-father) | unlikely |
| 49105970 | CCDC22 | NM_014008 | c.1636G >A | p.Asp546Asn | Missense | rs147222955 | 0/0.048 | 23 | tolerated | damaging | 0.625 | neutral | 1/155 male | yes (grand-father) | unlikely | |
| 49142473 | PPP1R3F | NM_033215 | c.1321G >A | p.Glu441Lys | Missense | — | -/- | 56 | deleterious | benign | 0.153 | neutral | 0/384 | yes (grand-father) | possible | |
| 53630356 | HUWE1 | NM_031407 | c.2849T >A | p.Val950Asp | Missense | — | -/- | 152 | deleterious | damaging | 0.702 | neutral | 0/329 male | no (grand-father) | probable | |
| 75649236 | MAGEE1 | NM_020932 | c.913A >T | p.Ser305Cys | Missense | rs142080557 | 0/0.16 | 112 | tolerated | damaging | 0.309 | neutral | yes (grand-father) | unlikely | ||
| Family 5 | 117251283 | KLHL13 | NM_033495 | c.-132040G >A | 5'UTR | — | -/- | 0/71 male | NA | unknown | ||||||
| 138287146 | FGF13 | NM_004114 | c.-493981G >A | 5'UTR | rs185138825 | 0/- | 3/73 male | NA | unlikely | |||||||
| Family 6 | 152960226 | SLC6A8 | NM_005629 | c.1649C >G | p.Thr550Ser | Missense | — | -/0.01 | 58 | tolerated | damaging | 0.284 | neutral | 0/218 male | yes (grand-father) | possible |
| 153210180 | RENBP | NM_002910 | c.-134_-118delins17 | 5'UTR | — | -/- | yes (grand-father) | unknown | ||||||||
| 153701511 | PLXNA3 | NM_017514 | c.*483 G >A | 3'UTR | rs41311390 | 0.3/- | yes (grand-father) | unknown | ||||||||
| 48432832 | RBM3 | NM_006743 | c.-143C >G | 5'UTR | — | -/- | yes (grand-father) | unknown | ||||||||
| 152989468 | BCAP31 | NM_001139457 | c.-350_-349insCA | 5'UTR ins | — | -/- | yes (grand-father) | unknown | ||||||||
| Family 7 | 120009218 | CT47B1 | NM_001145718 | c.291_293del | p.Glu99del | Inframe del | — | -/- | 3/40 male | NA | unlikely | |||||
| Family 8 | 3227525 | MXRA5 | NM_015419 | c.*232 G >T | 3'UTR | rs143753500 | 0/- | no (2 uncles) | unknown | |||||||
| 8499107 | KAL1 | NM_000216 | c.*1929 A >G | 3'UTR | rs6530183 | 0/- | yes (2 uncles) | unknown | ||||||||
| 53117400 | TSPYL2 | NM_022117 | c.*279 A >C | 3'UTR | rs113822334 | 0.9/- | no (2 uncles) | unknown | ||||||||
| 53966801 | PHF8 | NM_001184896 | c.2904_2906del | p.Ser969del | Inframe del | — | — | 0/189 | no (2 uncles) | probable | ||||||
| 63412635 | FAM123B | NM_152424 | c.532C >T | p.Arg178Cys | Missense | — | −/0.01 | 180 | deleterious | damaging | 0.506 | neutral | no (2 uncles) | unlikely | ||
| 153037579 | PLXNB3 | NM_005393 | c.2739–58_2739–57ins28 | Intronic ins | — | -/- | yes (2 uncles) | unlikely | ||||||||
| 47466513 | SYN1 | NM_006950 | c.435+27 G >C | Intronic | — | −/0.26 | no (2 uncles) | unlikely | ||||||||
| 55027965 | APEX2 | NM_014481 | c.158–5del | Intronic del | — | -/- | yes (2 uncles) | unlikely | ||||||||
| 154284285 | FUNDC2 | NM_023934 | c.*1338C >G | 3'UTR | rs146616394 | 0/- | yes (2 uncles) | unknown | ||||||||
| Family 9 | 153210180 | RENBP | NM_002910 | c.-134_-118delins17 | 5'UTR | — | -/- | yes (grand-father) | unknown | |||||||
| 154754246 | TMLHE | NM_018196 | c.229C >T | p.Arg77X | Nonsense | — | -/- | 0/508 male, 1 htz/184 female | no (grand-father and uncle) | probable | ||||||
| Family 11 | 54956008 | TRO | NM_001039705 | c.2851 G >A | p.Gly951Ser | Missense | — | -/- | 56 | deleterious | unknown | 0.174 | neutral | 0/138 male | yes (heathy brother) | possible |
| Family 12 | 151123143 | GABRE | NM_004961 | c.*30C >T | 3'UTR | — | -/- | NA | unknown |
Abbreviation: MAF, minor allele frequency; SIFT, scale-invariant feature transform; UTR, untranslated region.
This list includes variants that are rare or absent from databases (MAFs <1%), are found in genes expressed in brain and have a possible impact on gene or protein function (nonsense, missense, predicted to be deleterious by at least one bioinformatics algorithm or in an intron, 5'UTR or 3'UTR with a predicted effect on a splice site or promoter). Mutpred: score <0.5: benign; 0.5–0.75: possibly disease-associated; and >0.75: probably disease-associated.Grantham distance: conservative (0–50), moderately conservative (51–100), moderately radical (101–150) or radical (⩾151).