NM_000156.6(GAMT):c.64dup (p.Ala22fs) AND Cerebral creatine deficiency syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 24, 2022
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:: RCV001908704.4

Allele description [Variation Report for NM_000156.6(GAMT):c.64dup (p.Ala22fs)]

NM_000156.6(GAMT):c.64dup (p.Ala22fs)

Genes:

LOC130062945:ATAC-STARR-seq lymphoblastoid silent region 9707 [Gene]
GAMT:guanidinoacetate N-methyltransferase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000156.6(GAMT):c.64dup (p.Ala22fs)

Other names:

NM_000156.6(GAMT):c.64dup; p.Ala22fs

HGVS:

NC_000019.10:g.1401418dup
NG_009785.1:g.5141dup
NM_000156.6:c.64dupMANE SELECT
NM_138924.3:c.64dup
NP_000147.1:p.Ala22fs
NP_620279.1:p.Ala22fs
NC_000019.9:g.1401411_1401412insC
NC_000019.9:g.1401417dup

Protein change:

A22fs

Links:

dbSNP: rs1569009071

NCBI 1000 Genomes Browser:

rs1569009071

Molecular consequence:

NM_000156.6:c.64dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_138924.3:c.64dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002168859	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27650626, 15108290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002168859

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 24, 2022)

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

Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

Pacheva I, Ivanov I, Penkov M, Kancheva D, Jordanova A, Ivanova M.

Ann Clin Lab Sci. 2016 Sep;46(5):557-61.

PubMed [citation]

PMID:: 27650626

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, SCV002168859.3

#	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: 1402763). This variant is also known as p.A22fsX19. This premature translational stop signal has been observed in individual(s) with guanidinoacetate methyltransferase (GAMT) deficiency (PMID: 15108290, 27650626). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala22Glyfs*63) 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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