Submissions for variant NM_002700.3(POU4F3):c.403C>T (p.Pro135Ser)

gnomAD frequency: 0.00002  dbSNP: rs200286254

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151674	SCV000199957	uncertain significance	not specified	2014-04-04	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Pro135Ser varia nt in POU4F3 has not been previously reported in individuals with hearing loss, but has been identified in 0.02% (2/8598) of European American chromosomes by th e NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs200 286254). Computational prediction tools and conservation analyses suggest that t he Pro135Ser variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significan ce of this variant cannot be determined with certainty; however based upon the c omputational data and the presence of the variant in the general population, we would lean towards a more likely benign role.
GeneDx	RCV001753535	SCV001986398	uncertain significance	not provided	2019-06-28	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV000477930	SCV002785117	uncertain significance	Autosomal dominant nonsyndromic hearing loss 15	2021-07-15	criteria provided, single submitter	clinical testing
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477930	SCV000536859	uncertain significance	Autosomal dominant nonsyndromic hearing loss 15	2015-10-09	no assertion criteria provided	research