U.S. flag

An official website of the United States government

NM_000156.6(GAMT):c.701C>T (p.Thr234Ile) AND Deficiency of guanidinoacetate methyltransferase

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 6, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV002305524.2

Allele description [Variation Report for NM_000156.6(GAMT):c.701C>T (p.Thr234Ile)]

NM_000156.6(GAMT):c.701C>T (p.Thr234Ile)

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.701C>T (p.Thr234Ile)
Other names:
NM_000156.6(GAMT):c.701C>T; p.Thr234Ile
HGVS:
  • NC_000019.10:g.1397369G>A
  • NG_008283.1:g.18486G>A
  • NG_009785.1:g.9185C>T
  • NM_000156.6:c.701C>TMANE SELECT
  • NP_000147.1:p.Thr234Ile
  • NC_000019.9:g.1397368G>A
  • NM_000156.5:c.701C>T
Protein change:
T234I
Links:
dbSNP: rs1401966018
NCBI 1000 Genomes Browser:
rs1401966018
Molecular consequence:
  • NM_000156.6:c.701C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Deficiency of guanidinoacetate methyltransferase (CCDS2)
Synonyms:
CEREBRAL CREATINE DEFICIENCY SYNDROME 2
Identifiers:
MONDO: MONDO:0012999; MedGen: C0574080; Orphanet: 382; OMIM: 612736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002600162ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen_CCDS_ACMG_Specifications_GAMT_v1.1)		Uncertain significance
(Jun 6, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen, SCV002600162.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000156.6:c.701C>T variant in GAMT is a missense variant predicted to cause substitution of threonine by isoleucine at amino acid 234 (p.Thr234Ile). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00011 (1/126040) in the African / African American population, which is lower than the ClinGen CCDS VCEP's threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.268 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAMT function (BP4). To our knowledge, this variant has not been reported in the published literature. It has been previously noted in ClinVar (ID 544252). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes VCEP (Specifications Version 1.1.0): PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

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

Last Updated: Sep 29, 2024