Table 1.
Summary of the four POU4F3 variants identified in this study.
| Family | Nucleotide change | Amino acid change | hom/het | Allele frequency∗ | Pathogenicity | ACMG code | Computational evidence | Origin of variant | Cosegregation | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SIFT | PolyPhen | Mutation assessor | |||||||||
| A | c.696G>T | p.(Glu232Asp) | het | 0.0001 | Likely pathogenic | PM1+PM2+PM5+PP1+PP3 | Deleterious | Probably damaging | High | De novo | Yes |
| B | c.325C>T | p.(His109Tyr) | het | — | Uncertain significance | PP1 | Tolerated | Benign | Medium | De novo | Yes |
| C | c.635T>C | p.(Leu212Pro) | het | — | Likely pathogenic | PM1+PM2+PP1+PP3 | Deleterious | Probably damaging | High | De novo | Yes |
| D | c.183delG | p.(Ala62Argfs∗22) | het | — | Pathogenic | PVS1+PM2+PP1 | De novo | Yes | |||
∗Allele frequency in East Asia reported by ExAC. hom: homozygous; het: heterozygous; —: no data. Notes: PVS1: null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single, or multiexon deletion) in a gene where loss of function (LOF) is a known mechanism of disease; PM1: located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation; PM2: a variant is absent from a large general population or a control cohort; PM5: novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before; PP1: segregation of a variant in a family; PP3: multiple lines of computational evidence support a deleterious effect on the gene or gene product.