ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.471T>G (p.Phe157Leu)

gnomAD frequency: 0.00003  dbSNP: rs372260609
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000611035 SCV000731131 likely benign not specified 2017-11-08 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.
Invitae RCV000706494 SCV000835548 uncertain significance Cerebral creatine deficiency syndrome 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 157 of the GAMT protein (p.Phe157Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs372260609, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect GAMT function (PMID: 26003046). 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.

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