ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.139G>A (p.Gly47Arg)

gnomAD frequency: 0.00001  dbSNP: rs121964982
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622444 SCV000741346 uncertain significance Inborn genetic diseases 2016-03-04 criteria provided, single submitter clinical testing
Invitae RCV000012755 SCV000827129 pathogenic Non-ketotic hyperglycinemia 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 47 of the AMT protein (p.Gly47Arg). This variant is present in population databases (rs121964982, gnomAD 0.009%). This missense change has been observed in individual(s) with glycine encephalopathy (PMID: 8005589, 27362913; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11975). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AMT protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AMT function (PMID: 23352163). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000012755 SCV004196246 likely pathogenic Non-ketotic hyperglycinemia 2023-08-29 criteria provided, single submitter clinical testing
OMIM RCV003230354 SCV000032990 pathogenic Glycine encephalopathy 2 1994-06-01 no assertion criteria provided literature only

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