ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.139G>A (p.Gly47Arg) (rs121964982)

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Total submissions: 3
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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 Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Invitae RCV000012755 SCV000827129 pathogenic Non-ketotic hyperglycinemia 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 47 of the AMT protein (p.Gly47Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs121964982, ExAC 0.009%). This variant has been observed to segregate with atypical glycine encephalopathy in two siblings (PMID: 8005589) and has been reported in trans with another AMT variant in several individuals affected with glycine encephalopathy (PMID: 27362913, Invitae). ClinVar contains an entry for this variant (Variation ID: 11975). Experimental studies have shown that this missense change results in an protein with severely diminished enzymatic activity (PMID: 23352163). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012755 SCV000032990 pathogenic Non-ketotic hyperglycinemia 1994-06-01 no assertion criteria provided literature only

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