Table 3.
Functional prediction for TMPRSS3 missense variants found in Pakistani families in this study
| Variant | SIFT | PolyPhen-2 | PhyloP a | ConSeq b | PROSITE |
|---|---|---|---|---|---|
| c.310G>A (p.Glu104Lys) |
Affect protein function |
Probably damaging |
4.41 | 9 (f) | LDLRA domain signature, tyrosine kinase phosphorylation site |
| c.767C>T (p.Ala256Val) |
Affect protein function |
Probably damaging |
6.26 | 9 (s) | Histidine active site, adjacent to charge relay system |
| c.1219T>C (p.Cys407Arg) c |
Affect protein function |
Probably damaging |
4.92 | 7 (b) | Disulfide bridge, adjacent to serine active site |
| c.1273T>C (p.Cys425Arg) |
Affect protein function |
Probably damaging |
4.92 | 9 (s) | Disulfide bridge, N-myristoylation site |
a
Vertebrate Basewise Conservation for 44 species by PhyloP (phyloP44wayAll) from the UCSC Genome Browser, Build 36. Positive scores are assigned for nucleotides that are predicted to be conserved and represent −log p-values under a null hypothesis of neutral evolution.
b
ConSeq conservation scale ranges from 9 for conserved to 1 for variable. e = exposed; b = buried; f = functional (highly conserved and exposed); s = structural (highly conserved and buried)
c
The p.Cys407Arg variant was first reported by Ben-Yosef et al. (9)