Submissions for variant NM_004279.3(PMPCB):c.1462C>T (p.Arg488Cys)

gnomAD frequency: 0.00101  dbSNP: rs151236121

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001839096	SCV002099000	uncertain significance	Multiple mitochondrial dysfunctions syndrome 6	2021-03-24	criteria provided, single submitter	clinical testing	The heterozygous c.1462C>T (p.Arg488Cys) missense variant identified in exon 13 (of 13) of the PMPCB gene has not been reported in affected individualsthe literature. The variant has 0.0009536 allele frequency in the gnomAD(v3) database (145 out of 152048 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database.The affected Arg488 is the second to the last residue of the PMPCB protein (a 489 amino acid protein) and is predicted “deleterious”by multiple in silico tools. Based on the available evidence, the heterozygous c.1462C>T (p.Arg488Cys) missense variant identified in the PMPCB gene is reported as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002542820	SCV003513059	likely benign	not provided	2023-12-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003956407	SCV004773873	likely benign	PMPCB-related disorder	2022-07-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).