Submissions for variant NM_032520.5(GNPTG):c.7G>A (p.Ala3Thr)

gnomAD frequency: 0.00057  dbSNP: rs914207699

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000665343	SCV000789449	uncertain significance	GNPTG-mucolipidosis	2017-02-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000665343	SCV000894975	uncertain significance	GNPTG-mucolipidosis	2018-10-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000665343	SCV002045562	uncertain significance	GNPTG-mucolipidosis	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002530653	SCV003260318	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3 of the GNPTG protein (p.Ala3Thr). This variant is present in population databases (no rsID available, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with GNPTG-related conditions. ClinVar contains an entry for this variant (Variation ID: 550565). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Breakthrough Genomics, Breakthrough Genomics	RCV002530653	SCV005194089	uncertain significance	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004768521	SCV005381585	likely benign	not specified	2024-08-02	criteria provided, single submitter	clinical testing	Variant summary: GNPTG c.7G>A (p.Ala3Thr) results in a non-conservative amino acid change in 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 0.00011 in 1317162 control chromosomes, predominantly at a frequency of 0.0019 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.075 fold of the estimated maximal expected allele frequency for a pathogenic variant in GNPTG causing Mucolipidosis III Gamma phenotype (0.0018). To our knowledge, no occurrence of c.7G>A in individuals affected with Mucolipidosis III Gamma and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 550565). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003965425	SCV004785144	likely benign	GNPTG-related disorder	2023-08-08	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).