Submissions for variant NM_000151.4(G6PC1):c.132C>T (p.Tyr44=)

gnomAD frequency: 0.00004  dbSNP: rs202190197

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000428742	SCV000513087	likely benign	not specified	2016-10-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000428742	SCV000917381	benign	not specified	2018-07-02	criteria provided, single submitter	clinical testing	Variant summary: G6PC c.132C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0012 in 121408 control chromosomes, predominantly at a frequency of 0.0078 within the South Asian subpopulation in the ExAC database. The observed variant frequency within South Asian control individuals in the ExAC database is approximately 5-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in G6PC causing Glycogen Storage Disease Type Ia phenotype (0.0017), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.132C>T in individuals affected with Glycogen Storage Disease Type Ia and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV000966422	SCV001113742	benign	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2024-01-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000966422	SCV002804699	likely benign	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2021-10-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003168625	SCV003911685	likely benign	Inborn genetic diseases	2023-01-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics, part of Exact Sciences	RCV003912618	SCV004731099	benign	G6PC1-related condition	2022-02-08	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV000966422	SCV001459071	benign	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2020-01-04	no assertion criteria provided	clinical testing