NM_000156.6(GAMT):c.670G>A (p.Ala224Thr) AND Cerebral creatine deficiency syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000529306.5

Allele description [Variation Report for NM_000156.6(GAMT):c.670G>A (p.Ala224Thr)]

NM_000156.6(GAMT):c.670G>A (p.Ala224Thr)

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.670G>A (p.Ala224Thr)
Other names:
p.A224T:GCC>ACC
HGVS:
  • NC_000019.10:g.1397400C>T
  • NG_008283.1:g.18517C>T
  • NG_009785.1:g.9154G>A
  • NM_000156.6:c.670G>AMANE SELECT
  • NP_000147.1:p.Ala224Thr
  • NC_000019.9:g.1397399C>T
  • NM_000156.4:c.670G>A
  • NM_000156.5:c.670G>A
  • NM_138924.1:c.*1276G>A
  • Q14353:p.Ala224Thr
Protein change:
A224T
Links:
UniProtKB: Q14353#VAR_075303; dbSNP: rs141471799
NCBI 1000 Genomes Browser:
rs141471799
Molecular consequence:
  • NM_000156.6:c.670G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cerebral creatine deficiency syndrome (CCAD)
Synonyms:
Creatine deficiency syndromes
Identifiers:
MONDO: MONDO:0000456; MedGen: CN227588; Orphanet: 79172; OMIM: PS300352

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000659573Invitaecriteria provided, single submitter
Uncertain significance
(Nov 27, 2019)
germlineclinical testing

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000659573.5

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

Description

This sequence change replaces alanine with threonine at codon 224 of the GAMT protein (p.Ala224Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs141471799, ExAC 0.04%). This variant has not been reported in the literature in individuals with GAMT-related disease. ClinVar contains an entry for this variant (Variation ID: 205593). Experimental studies, in vitro, have shown that this missense change does not disrupt GAMT protein 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: Aug 17, 2021

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