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NM_000156.6(GAMT):c.526G>T (p.Glu176Ter) AND Cerebral creatine deficiency syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 20, 2023
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:
RCV001378842.7

Allele description [Variation Report for NM_000156.6(GAMT):c.526G>T (p.Glu176Ter)]

NM_000156.6(GAMT):c.526G>T (p.Glu176Ter)

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.526G>T (p.Glu176Ter)
Other names:
p.E176*:GAG>TAG
HGVS:
  • NC_000019.10:g.1398960C>A
  • NG_009785.1:g.7594G>T
  • NM_000156.6:c.526G>TMANE SELECT
  • NM_138924.3:c.526G>T
  • NP_000147.1:p.Glu176Ter
  • NP_620279.1:p.Glu176Ter
  • NC_000019.9:g.1398959C>A
  • NM_000156.4:c.526G>T
  • NM_138924.1:c.526G>T
Protein change:
E176*
Links:
dbSNP: rs796052525
NCBI 1000 Genomes Browser:
rs796052525
Molecular consequence:
  • NM_000156.6:c.526G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_138924.3:c.526G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001576519Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 20, 2023) 		germlineclinical testing

PubMed (4)
[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

Characterization of seven novel mutations in seven patients with GAMT deficiency.

Item CB, Mercimek-Mahmutoglu S, Battini R, Edlinger-Horvat C, Stromberger C, Bodamer O, Mühl A, Vilaseca MA, Korall H, Stöckler-Ipsiroglu S.

Hum Mutat. 2004 May;23(5):524.

PubMed [citation]
PMID:
15108290

Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids.

Engelke UF, Tassini M, Hayek J, de Vries M, Bilos A, Vivi A, Valensin G, Buoni S, Zannolli R, Brussel W, Kremer B, Salomons GS, Veendrick-Meekes MJ, Kluijtmans LA, Morava E, Wevers RA.

NMR Biomed. 2009 Jun;22(5):538-44. doi: 10.1002/nbm.1367.

PubMed [citation]
PMID:
19288536
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576519.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the C-terminus of the GAMT protein. Other variant(s) that disrupt this region (p.Gln193*, p.Glu176Serfs*2, p.Glu176Glyfs*15) have been observed in individuals with GAMT-related conditions (PMID: 15108290, 19288536, 23234264). This suggests that this may be a clinically significant region of the protein. ClinVar contains an entry for this variant (Variation ID: 205586). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu176*) in the GAMT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 61 amino acid(s) of the GAMT protein.

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

Last Updated: Sep 29, 2024