ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.626C>T (p.Thr209Met) (rs17851582)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000117117 SCV000168636 benign not specified 2013-05-28 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.
PreventionGenetics,PreventionGenetics RCV000117117 SCV000302738 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000020144 SCV000483720 benign Deficiency of guanidinoacetate methyltransferase 2018-03-06 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000272863 SCV000483721 likely benign Leigh syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000311501 SCV000483722 likely benign Mitochondrial complex I deficiency 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000715403 SCV000846232 benign History of neurodevelopmental disorder 2017-02-10 criteria provided, single submitter clinical testing General population or sub-population frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000676877 SCV000883934 benign not provided 2017-08-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000117117 SCV000919413 benign not specified 2018-11-09 criteria provided, single submitter clinical testing Variant summary: GAMT c.626C>T (p.Thr209Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.076 in 273748 control chromosomes in the gnomAD database, including 972 homozygotes. The observed variant frequency is approximately 70 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAMT causing Guanidinoactetate methyltransferase deficiency phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.626C>T in individuals affected with Guanidinoactetate methyltransferase deficiency has been reported. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Battini 2002). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as benign (1x)/likely benign(1x). Based on the evidence outlined above, the variant was classified as likely benign.
GeneReviews RCV000020144 SCV000040471 benign Deficiency of guanidinoacetate methyltransferase 2011-08-18 no assertion criteria provided curation Converted during submission to Benign.
Genetic Services Laboratory, University of Chicago RCV000117117 SCV000151278 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000676877 SCV000802691 benign not provided 2016-02-19 no assertion criteria provided clinical testing

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