ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.167C>T (p.Ala56Val)

gnomAD frequency: 0.00003  dbSNP: rs575350720
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655361 SCV000777291 uncertain significance Cerebral creatine deficiency syndrome 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 56 of the GAMT protein (p.Ala56Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 544255). 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 not expected to disrupt GAMT 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 RCV002060782 SCV002495784 uncertain significance Deficiency of guanidinoacetate methyltransferase 2021-03-30 criteria provided, single submitter clinical testing GAMT NM_000156.5 exon 1 p.Ala56Val (c.167C>T): This variant has not been reported in the literature but is present in 0.02% (3/13658) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-1401310-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:544255). This variant amino acid Valine (Val) is present in >30 species including mammals 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 RCV004972834 SCV005588541 uncertain significance Inborn genetic diseases 2024-10-25 criteria provided, single submitter clinical testing The c.167C>T (p.A56V) alteration is located in exon 1 (coding exon 1) of the GAMT gene. This alteration results from a C to T substitution at nucleotide position 167, causing the alanine (A) at amino acid position 56 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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