Submissions for variant NM_002700.3(POU4F3):c.553C>T (p.Arg185Cys)

gnomAD frequency: 0.00001  dbSNP: rs746613906

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001199348	SCV001370435	uncertain significance	Autosomal dominant nonsyndromic hearing loss 15	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001199348	SCV002768025	uncertain significance	Autosomal dominant nonsyndromic hearing loss 15	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant, NM_002700.2(POU4F3):c.553C>T, has been identified in exon 2 of 2 of the POU4F3 gene. The variant is predicted to result in a major amino acid change from arginine to cysteine at position 185 of the protein (NP_002691.1(POU4F3):p.Arg185Cys). The arginine residue at this position has moderate conservation (100 vertebrates, UCSC), and is located within the POU-specific functional domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.00040% (1 heterozygote). The variant has been previously described as a VUS (ClinVar, Deafnessvariationdatabase). An alternative change to glycine, has also been reported as a VUS (Deafnessvariationdatabase). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415146	SCV000492665	uncertain significance	Congenital sensorineural hearing impairment	2016-02-12	no assertion criteria provided	clinical testing