Table 1.
Rare Variants in PAX6 or SCL38A8 Predicted to be Potentially Damaging
| Position at | Nucleotide Acid | Amino Acid | REVEL | CADD | SIFT | Polyphen-2 | PROVEAN | GnomAD | Family | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variants | Exon | chr | change | Effect | Score | Score | Score | Score | Pred | Allele | ID | HGMD |
| A. PAX6 ( chr11, NM_000280.5) | ||||||||||||
| 1 | 5 | 31824280 | c.113G>C | p.Arg38Pro | 0.959 | 29.2 | D (0.001) | PD (0.998) | D | / | 7822 | DM |
| 2 | 5 | 31824265 | c.128C>T | p.Ser43Phe | 0.963 | 28.5 | D (0.000) | PD (0.999) | D | / | 8407 | DM |
| 3 | 6 | 31823324 | c.142G>A | p.Val48Met | 0.952 | 32 | D (0.000) | PD (1.000) | D | / | 8453 | / |
| 4 | 6 | 31823324 | c.142G>T | p.Val48Leu | 0.968 | 33 | D (0.001) | PD (1.000) | D | / | 8465 | / |
| 5 | 6 | 31823252 | c.214G>T | p.Gly72Cys | 0.984 | 31 | D (0.000) | PD (1.000) | D | 1/31404 | 4012 | DM |
| 6 | 6 | 31823252 | c.214G>A | p.Gly72Ser | 0.974 | 29.2 | D (0.001) | PD (0.995) | D | / | 16526 | DM |
| 7 | 6 | 31823237 | c.229A>G | p.Arg77Gly | 0.936 | 24.8 | D (0.000) | PD (0.981) | D | / | 5538 | / |
| 8 | 6 | 31823233 | c.233T>G | p.Val78Gly | 0.566 | 27.9 | D (0.000) | PD (1.000) | D | / | 14014 | DM |
| 9 | 6 | 31823231 | c.235G>C | p.Ala79Pro | 0.594 | 27.4 | D (0.001) | PD (0.998) | D | / | 17508 | / |
| 10 | 6 | 31823170 | c.296C>T | p.Ala99Val | 0.950 | 28.8 | D (0.001) | PD (0.999) | D | / | 20011 | / |
| 11 | 7 | 31822404 | c.358G>A | p.Val120Met | 0.891 | 32 | D (0.000) | PD (1.000) | N | / | 10675 | / |
| 12 | 7 | 31822379 | c.383G>T | p.Arg128Leu | 0.908 | 24.6 | D (0.000) | B (0.280) | D | / | 17516 | / |
| 13 | 7 | 31822379 | c.383G>A | p.Arg128His | 0.933 | 28.1 | D (0.000) | PB (0.773) | D | / | 18734 | / |
| 14 | 8 | 31816238 | c.622C>T | p.Arg208Trp | 0.877 | 29.4 | D (0.000) | PD (1.000) | D | 1/251466 | 7721; 6565 | DM |
| 15 | 10 | 31815345 | c.771G>T | p.Trp257Cys | 0.956 | 32 | D (0.000) | PD (1.000) | D | / | 17267 | / |
| 16 | 13 | 31811483 | c.1268A>T | p.*423Leuext*14 | / | / | / | / | / | / | 14860; 4926 | DM |
| B. SLC38A8 (chr16, NM_001080442.3) | ||||||||||||
| 1 | 2 | 84075752 | c.11delA | p.Gln4Argfs*31 | / | / | / | / | / | / | 15394 | / |
| 2 | 6 | 84063109 | c.680T>A | p.Phe227Tyr | 0.647 | 29.4 | D (0.000) | PD (1.000) | D | 53/282750 | 4517 | / |
| 3 | 6 | 84063107 | c.682G>C | p.Gly228Arg | 0.625 | 28.9 | D (0.001) | PD (1.000) | D | 5/282722 | 141 | / |
| 4 | 6 | 84063100 | c.689A>G | p.Gln230Arg | 0.532 | 33 | D (0.004) | PD (1.000) | D | / | 141 | / |
| 5 | 7 | 84056488 | c.697G>A | p.Glu233Lys | 0.792 | 25.6 | T (0.245) | PD (1.000) | N | 20/266328 | 15394;14534;20140 | DM† |
| 6 | 10 | 84046650 | c.1170C>A | p.Cys390* | / | / | / | / | / | / | 4517 | / |
Note: For PAX6 in gnomAD, 5% variants had REVEL or CADD scores greater than 0.88 or 29.9, while 75% had such scores less than 0.61 or 24.
For SLC38A8 in gnomAD, 5% variants had REVEL or CADD scores greater than 0.56 or 28.4, while 75% had such scores less than 0.34 or 24.2.
PD = probably damaging; PB = possibly damaging; D = damaging; B = benign; T = tolerant; N = neutral; DM = damaging mutation; PolyPhen-2 version 2.2.2.
†
The c.697G>A is a well-defined pathogenic variant reported in previous study (Poulter JA, et al. Am J Hum Genet 2013;93:1143-1150).