ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.20C>A (p.Thr7Asn)

gnomAD frequency: 0.00001  dbSNP: rs761687649
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000350120 SCV000410919 uncertain significance Deficiency of guanidinoacetate methyltransferase 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001245927 SCV001419251 uncertain significance Cerebral creatine deficiency syndrome 2022-05-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 7 of the GAMT protein (p.Thr7Asn). This variant is present in population databases (rs761687649, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 328354). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000350120 SCV002495785 uncertain significance Deficiency of guanidinoacetate methyltransferase 2021-03-30 criteria provided, single submitter clinical testing GAMT NM_000156.5 exon 1 p.Thr7Asn (c.20C>A): This variant has not been reported in the literature but is present in 0.001% (1/67948) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-1401457-G-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:328354). This variant amino acid Asparagine (Asn) is present in the Megabat and the Black Flying Fox and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004021739 SCV004873730 uncertain significance Inborn genetic diseases 2023-09-20 criteria provided, single submitter clinical testing The c.20C>A (p.T7N) alteration is located in exon 1 (coding exon 1) of the GAMT gene. This alteration results from a C to A substitution at nucleotide position 20, causing the threonine (T) at amino acid position 7 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000350120 SCV002087066 uncertain significance Deficiency of guanidinoacetate methyltransferase 2019-10-28 no assertion criteria provided clinical testing

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