Submissions for variant NM_000481.4(AMT):c.1112G>A (p.Arg371His)

dbSNP: rs147006017

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638268	SCV000759755	likely benign	Glycine encephalopathy	2024-10-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001090580	SCV001246194	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000638268	SCV001306997	uncertain significance	Glycine encephalopathy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Breakthrough Genomics, Breakthrough Genomics	RCV001090580	SCV005189565	uncertain significance	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782482	SCV005395153	uncertain significance	not specified	2024-09-09	criteria provided, single submitter	clinical testing	Variant summary: AMT c.1112G>A (p.Arg371His) results in a non-conservative amino acid change located in the Glycine cleavage T-protein, C-terminal barrel domain (IPR013977) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 251444 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in AMT causing Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) (0.00038 vs 0.0014), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1112G>A in individuals affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 531761). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc.	RCV000638268	SCV002081692	uncertain significance	Glycine encephalopathy	2019-10-28	no assertion criteria provided	clinical testing
GenomeConnect - Brain Gene Registry	RCV000638268	SCV002107385	not provided	Glycine encephalopathy		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 2/21/2020 by Lab or GTR ID 500057. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator John Constantino MD PhD from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.