Table 2.
In-silico pathogenicity prediction analysis of NAV3 variants
| Pathogenic predictors | p.(Arg2261Cys) | p.(Ser1326Asn) | p.(Ser1681Arg) | p.(Thr1617Tyrfs*9) | p.(Asp1208Argfs*58) | p.(Trp332*) | p.(Trp2270*) |
|---|---|---|---|---|---|---|---|
| gnomAD | 0.0000201 | NDA | NDA | NDA | NDA | NDA | NDA |
| CADD | 34 | 25.2 | 26.1 | NA | NA | 41 | 54 |
| MTR | 0.9 | 0.87 | 0.86 | NA | NA | NA | NA |
| MetaDome | Slightly tolerant | Slightly intolerant | Slightly intolerant | NA | NA | NA | NA |
| GERP++ | 5.4 | 5.96 | 4.49 | NA | NA | 5.5 | 5.4 |
| M-CAP | Damaging | Tolerated | Damaging | NA | NA | NA | NA |
| SIFT | Tolerated | Damaging | Damaging | NA | NA | NA | NA |
| MutationTaster | Disease causing | Disease causing | Disease causing | NA | NA | Disease-causing | Disease-causing |
| Provean | Pathogenic | Uncertain | Pathogenic | NA | NA | NA | NA |
| Polyphen-2 HumDiv | Probably Damaging | Probably damaging | Probably damaging | NA | NA | NA | NA |
| ACMG classification | BP1a, BP4b, PM2c | BP1a, BP4b, PM2c | BP1a, BP4b, PM2c | PVS1d, PM2c | PM2c | PVS1d, PM2c | PM2c |
NDA no data available, NA not applicable.
aBP1 = Missense variant in a gene for which primarily truncating variants are known to cause disease. (Benign, Supporting).
bBP4 = MetaRNN = 0.415 is between 0.267 and 0.43.
c PM2 Variant not found in gnomAD genomes.
dPVS1 = Null variant (nonsense) in gene NAV3, predicted to cause NMD.