Submissions for variant NM_000122.2(ERCC3):c.1960G>A (p.Glu654Lys)

gnomAD frequency: 0.00013  dbSNP: rs568193912

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001462857	SCV001666784	likely benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258798	SCV002532614	uncertain significance	Xeroderma pigmentosum	2021-11-18	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120790	SCV002547833	benign	not specified	2022-05-26	criteria provided, single submitter	clinical testing	Variant summary: ERCC3 c.1960G>A (p.Glu654Lys) results in a conservative amino acid change located in the Helicase, C-terminal domain (IPR001650) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00046 in 251470 control chromosomes (gnomAD), predominantly at a frequency of 0.0037 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 33 fold of the estimated maximal expected allele frequency for a pathogenic variant in ERCC3 causing Xeroderma Pigmentosum phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV005328213	SCV005994142	likely benign	Inborn genetic diseases	2025-02-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ITMI	RCV000120790	SCV000084954	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV003915201	SCV004732607	likely benign	ERCC3-related disorder	2024-02-22	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).