NM_000156.6(GAMT):c.402C>A (p.Tyr134Ter) AND Cerebral creatine deficiency syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 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:: RCV001890336.4

Allele description [Variation Report for NM_000156.6(GAMT):c.402C>A (p.Tyr134Ter)]

NM_000156.6(GAMT):c.402C>A (p.Tyr134Ter)

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.402C>A (p.Tyr134Ter)

HGVS:

NC_000019.10:g.1399185G>T
NG_009785.1:g.7369C>A
NM_000156.6:c.402C>AMANE SELECT
NM_138924.3:c.402C>A
NP_000147.1:p.Tyr134Ter
NP_620279.1:p.Tyr134Ter
NC_000019.9:g.1399184G>T

Protein change:

Y134*

Links:

dbSNP: rs556829801

NCBI 1000 Genomes Browser:

rs556829801

Molecular consequence:

NM_000156.6:c.402C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_138924.3:c.402C>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002156808	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19027335, 15108290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002156808

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 8, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency.

Dhar SU, Scaglia F, Li FY, Smith L, Barshop BA, Eng CM, Haas RH, Hunter JV, Lotze T, Maranda B, Willis M, Abdenur JE, Chen E, O'Brien W, Wong LJ.

Mol Genet Metab. 2009 Jan;96(1):38-43. doi: 10.1016/j.ymgme.2008.10.008. Epub 2008 Nov 21.

PubMed [citation]

PMID:: 19027335

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002156808.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1382497). This premature translational stop signal has been observed in individual(s) with guanidinoacetate methyltransferase deficiency (PMID: 19027335). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Tyr134*) in the GAMT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAMT are known to be pathogenic (PMID: 15108290).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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