Submissions for variant NM_000156.6(GAMT):c.17C>T (p.Ala6Val)

dbSNP: rs796052529

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187582	SCV000241176	uncertain significance	not provided	2014-02-07	criteria provided, single submitter	clinical testing	p.Ala6Val (GCG>GTG): c.17 C>T in exon 1 of the GAMT gene (NM_000156.4) The Ala6Val missense change in the GAMT gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 3,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is conservative, as Alanine and Valine are both uncharged, non-polar amino acids. However, it alters a conserved position in the protein. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Ala6Val is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI,EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002517862	SCV003280792	uncertain significance	Cerebral creatine deficiency syndrome	2022-05-07	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 6 of the GAMT protein (p.Ala6Val). This variant is not present in population databases (gnomAD no frequency). 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: 205597). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV003258689	SCV003978650	uncertain significance	Inborn genetic diseases	2023-05-23	criteria provided, single submitter	clinical testing	The c.17C>T (p.A6V) 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 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV001828001	SCV002087067	uncertain significance	Deficiency of guanidinoacetate methyltransferase	2020-03-07	no assertion criteria provided	clinical testing