NM_000156.6(GAMT):c.587C>T (p.Ala196Val) AND Cerebral creatine deficiency syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 15, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000793466.12

Allele description

NM_000156.6(GAMT):c.587C>T (p.Ala196Val)

Gene:
GAMT:guanidinoacetate N-methyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_000156.6(GAMT):c.587C>T (p.Ala196Val)
Other names:
p.A196V:GCG>GTG
HGVS:
  • NC_000019.10:g.1397483G>A
  • NG_008283.1:g.18600G>A
  • NG_009785.1:g.9071C>T
  • NM_000156.6:c.587C>TMANE SELECT
  • NP_000147.1:p.Ala196Val
  • NC_000019.9:g.1397482G>A
  • NM_000156.4:c.587C>T
  • NM_000156.5:c.587C>T
  • NM_138924.1:c.*1193C>T
  • Q14353:p.Ala196Val
Protein change:
A196V
Links:
UniProtKB: Q14353#VAR_075302; dbSNP: rs565109128
NCBI 1000 Genomes Browser:
rs565109128
Molecular consequence:
  • NM_000156.6:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cerebral creatine deficiency syndrome (CCAD)
Synonyms:
Creatine deficiency syndromes
Identifiers:
MONDO: MONDO:0000456; MedGen: C5244016; Orphanet: 79172; OMIM: PS300352

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000932818Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 15, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene.

Mercimek-Mahmutoglu S, Pop A, Kanhai W, Fernandez Ojeda M, Holwerda U, Smith D, Loeber JG, Schielen PC, Salomons GS.

Gene. 2016 Jan 1;575(1):127-31. doi: 10.1016/j.gene.2015.08.045. Epub 2015 Aug 28.

PubMed [citation]
PMID:
26319512

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000932818.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 196 of the GAMT protein (p.Ala196Val). This variant is present in population databases (rs565109128, gnomAD 0.02%). 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: 205588). 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: 26319512). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024