Submissions for variant NM_000170.3(GLDC):c.1545G>A (p.Arg515=)

dbSNP: rs121964976

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000248102	SCV000302841	benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000248102	SCV000613526	benign	not specified	2017-06-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000530402	SCV000636357	benign	Non-ketotic hyperglycinemia	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000248102	SCV000919472	benign	not specified	2018-09-27	criteria provided, single submitter	clinical testing	Variant summary: GLDC c.1545G>A alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.022 in 277184 control chromosomes in the gnomAD database, including 99 homozygotes. The observed variant frequency is approximately 7-fold above the estimated maximal expected allele frequency for a pathogenic variant in GLDC causing Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) phenotype (0.0031), strongly suggesting that the variant is benign. c.1545G>A has been reported in the literature in an individual affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia), though this patient had two pathogenic mutations in trans, supporting a benign impact of the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV000530402	SCV001331500	likely benign	Non-ketotic hyperglycinemia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV001711527	SCV001941444	benign	not provided	2019-04-12	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001711527	SCV005225344	likely benign	not provided		criteria provided, single submitter	not provided
SingHealth Duke-NUS Institute of Precision Medicine	RCV000530402	SCV000853163	uncertain significance	Non-ketotic hyperglycinemia	2017-06-07	no assertion criteria provided	curation
Natera, Inc.	RCV000530402	SCV001457130	benign	Non-ketotic hyperglycinemia	2020-09-16	no assertion criteria provided	clinical testing