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NM_000156.6(GAMT):c.22C>A (p.Pro8Thr) AND Inborn genetic diseases

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 7, 2017
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:
RCV002317101.9

Allele description [Variation Report for NM_000156.6(GAMT):c.22C>A (p.Pro8Thr)]

NM_000156.6(GAMT):c.22C>A (p.Pro8Thr)

Genes:
LOC130062945:ATAC-STARR-seq lymphoblastoid silent region 9707 [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.22C>A (p.Pro8Thr)
Other names:
p.P8T:CCC>ACC; NM_000156.6(GAMT):c.22C>A
HGVS:
  • NC_000019.10:g.1401455G>T
  • NG_009785.1:g.5099C>A
  • NM_000156.6:c.22C>AMANE SELECT
  • NM_138924.3:c.22C>A
  • NP_000147.1:p.Pro8Thr
  • NP_620279.1:p.Pro8Thr
  • NC_000019.9:g.1401454G>T
  • NM_000156.4:c.22C>A
  • NM_000156.5:c.22C>A
  • Q14353:p.Pro8Thr
Protein change:
P8T
Links:
UniProtKB: Q14353#VAR_071775; dbSNP: rs776498025
NCBI 1000 Genomes Browser:
rs776498025
Molecular consequence:
  • NM_000156.6:c.22C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_138924.3:c.22C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000851583Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 7, 2017) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene.

Mercimek-Mahmutoglu S, Ndika J, Kanhai W, de Villemeur TB, Cheillan D, Christensen E, Dorison N, Hannig V, Hendriks Y, Hofstede FC, Lion-Francois L, Lund AM, Mundy H, Pitelet G, Raspall-Chaure M, Scott-Schwoerer JA, Szakszon K, Valayannopoulos V, Williams M, Salomons GS.

Hum Mutat. 2014 Apr;35(4):462-9. doi: 10.1002/humu.22511. Epub 2014 Mar 6.

PubMed [citation]
PMID:
24415674

Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene.

Desroches CL, Patel J, Wang P, Minassian B, Marshall CR, Salomons GS, Mercimek-Mahmutoglu S.

Mol Genet Genomics. 2015 Dec;290(6):2163-71. doi: 10.1007/s00438-015-1067-x. Epub 2015 May 24.

PubMed [citation]
PMID:
26003046

Details of each submission

From Ambry Genetics, SCV000851583.5

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

Description

The p.P8T variant (also known as c.22C>A), located in coding exon 1 of the GAMT gene, results from a C to A substitution at nucleotide position 22. The proline at codon 8 is replaced by threonine, an amino acid with highly similar properties. This alteration was found to be heterozygous in one individual with no identifiable second alteration in the GAMT gene who presented with severe global developmental delay, hypotonia, and intractable epilepsy of unknown etiology; however, the individual’s MRS imaging was not consistent with guanidinoacetate methyltransferase deficiency (GAMT-D) (Mercimek-Mahmutoglu S et al. Hum. Mutat., 2014 Apr; 35:462-9; Desroches CL et al. Mol. Genet. Genomics, 2015 Dec; 290:2163-71). In addition, functional studies suggested that the alteration did not impact GAMT enzyme activity (Mercimek-Mahmutoglu S et al. Hum. Mutat., 2014 Apr; 35:462-9; Desroches CL et al. Mol. Genet. Genomics, 2015 Dec; 290:2163-71). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 13, 2024