Table 2.
Missense SNPs in genes associated with hearing loss
|
SNP |
rs9493627 |
rs143282422 |
rs35887622 |
rs143796236 |
rs12980998 |
rs61734651 |
rs5756795 |
rs36062310 |
|---|---|---|---|---|---|---|---|---|
| Gene | EYA4 | CDH23 | GJB2 | FSCN2 | ANKRD24 | COL9A3 | TRIOBP | KLHDC7B |
| SNP characteristics | ||||||||
| Chr | 6 | 10 | 13 | 17 | 19 | 20 | 22 | 22 |
| Pos (hg19) | 133789728 | 73377112 | 20763620 | 79495969 | 4217510 | 61451332 | 38122122 | 50988105 |
| Locus | DFNA10 | DFNB12 |
DFNA3A DFNB1A |
– | – | – | DFNB28 | – |
| Alleles (major>minor) | G>A | G>A | A>G | C>T | A>T | C>T | T>C | G>A |
| MAF | 0.319 | 0.011 | 0.015 | 0.008 | 0.187 | 0.072 | 0.458 | 0.043 |
| AA change | p.Gly277Ser | p.Ala366Thr | p.Met34Thr | p.His138Tyr | p.Thr785Ser | p.Arg103Trp | p.Phe1187Leu | p.Val1145Met |
| Pathogenicity score | 0.29 | 0.43 | 0.71 | 0 | 1 | 0 | 1 | 0.71 |
| Phenotype | hearing loss, AD | hearing loss, AR/Usher syndrome | hearing loss, AD and AR | hearing loss in mice44 | abnormal ABR in mice23 | Stickler syndrome, AR | hearing loss, AR | abnormal ABR in mice23 |
| Gene characteristics | ||||||||
| Transcript | NM_004100.5 | NM_022124.6 | NM_00400.6 | NM_001077182.3 | NM_133475.1 | NM_001853.4 | NM_001039141.3 | – |
| Gene length (bp) | 5,699 | 10,085 | 2,250 | 1,665 | 4,026 | 2,485 | 10,129 | 2,990 |
| Translation length | 639 | 3,359 | 226 | 492 | 1,146 | 684 | 2,365 | 594 |
| Number of exons | 20 | 70 | 2 | 5 | 22 | 32 | 24 | 1 |
| Total variants gnomAD v2.1.1 | 1,081 | 6,088 | 345 | 836 | 1,793 | 2,251 | 3,281 | 609 |
| All ≥1% (total) | 14 | 84 | 4 | 1 | 48 | 54 | 38 | 7 |
| MAF ≥1% in EUR | 10 | 60 | 1 | 6 | 36 | 53 | 38 | 7 |
| Total unique gnomAD SNPs in same exon as GWAS SNP | 0 | 1 | 0 | 1 | 6 | 1 | 14 | 6 |
| Pathogenicity | ||||||||
| DM | 52 | 353 | 270 | 0 | 0 | 9 | 49 | 0 |
| DM? | 8 | 67 | 77 | 0 | 0 | 1 | 14 | 1 |
| SUM | 60 | 420 | 347 | 0 | 0 | 10 | 63 | 1 |
| Exon containing SNP | 11 | 11 | 2 | 1 | 18 | 5 | 7 | 1 |
Abbreviations: Chr, chromosome; Pos, genomic position; MAF, minor allele frequency in the current study; AA change, amino acid change; AD, autosomal dominant; AR, autosomal recessive; bp, base pair; EUR, European (non-Finnish); MAF, minor allele frequency; SNP, single-nucleotide polymorphism; DM, disease causing mutation. Pathogenicity score is estimated from an aggregated score detailed in Table S6. Aggregated pathogenicity score is normalized from 0 (variant predicted to be deleterious) to 1 (predicted to be benign). Phenotype: in humans, except where noted otherwise. DM?, likely disease causing mutation based on the Human Gene Mutation Database (HGMD) Professional version 2021.3.46