Submissions for variant NM_016239.4(MYO15A):c.4207-8C>G

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004785039	SCV005397492	uncertain significance	Autosomal recessive nonsyndromic hearing loss 3	2023-07-18	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (C>G) at the -8 position upstream of exon 11 of the MYO15A gene. This variant does not directly affect the amino acid sequence but is predicted to significantly impact MYO15A gene splicing. This is a novel variant that is absent from population datasets (gnomAD), databases of clinically annotated variants (ClinVar), and has not been reported in the literature in individuals with MYO15A-related disease, to our knowledge. Bioinformatic tools that predict splice site strength suggest that this variant would strongly impact splicing of exon 11, and the C nucleotide at this position is well conserved across the mammalian species examined. Functiol studies testing the effect of this variant on splicing have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this to be a variant of uncertain significance. ACMG Criteria: PM2, PP3