POU4F3 and deafness: When classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines19, POU4F3 p.Lys328Glu was predicted as deleterious by multiple in silico algorithms, meeting the PP3 category; it co-segregated with deafness in the family, fulfilling the PP1 category; it was absent from controls in multiple population databases and located in a critical functional domain, thus fitting the PM2 and PM1 categories, respectively; and most importantly, our in vitro functional studies demonstrated that this variant compromised protein function, fulfilling the PS3 category.