NM_000156.6(GAMT):c.144del (p.Tyr49fs) AND Cerebral creatine deficiency syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 12, 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:: RCV003747364.1

Allele description [Variation Report for NM_000156.6(GAMT):c.144del (p.Tyr49fs)]

NM_000156.6(GAMT):c.144del (p.Tyr49fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000156.6(GAMT):c.144del (p.Tyr49fs)

HGVS:

NC_000019.10:g.1401337del
NG_009785.1:g.5221del
NG_197362.1:g.158del
NM_000156.6:c.144delMANE SELECT
NM_138924.3:c.144del
NP_000147.1:p.Tyr49fs
NP_620279.1:p.Tyr49fs
NC_000019.9:g.1401332del
NC_000019.9:g.1401336del

Protein change:

Y49fs

Molecular consequence:

NM_000156.6:c.144del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_138924.3:c.144del - 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
SCV004506059	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21440503, 15108290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004506059

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 12, 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

Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.

Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, Erlichman C, Witzig TE.

Lancet Oncol. 2011 Apr;12(4):361-8. doi: 10.1016/S1470-2045(11)70062-6.

PubMed [citation]

PMID:: 21440503
PMCID:: PMC3106222

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 Invitae, SCV004506059.1

#	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. This premature translational stop signal has been observed in individual(s) with cerebral creatine deficiency syndrome (PMID: 21440503). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr49Ilefs*65) 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: Feb 28, 2024

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