NM_000156.6(GAMT):c.503A>C (p.Tyr168Ser) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Dec 5, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000493155.1

Allele description [Variation Report for NM_000156.6(GAMT):c.503A>C (p.Tyr168Ser)]

NM_000156.6(GAMT):c.503A>C (p.Tyr168Ser)

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.503A>C (p.Tyr168Ser)
HGVS:
  • NC_000019.10:g.1398983T>G
  • NG_009785.1:g.7571A>C
  • NM_000156.6:c.503A>CMANE SELECT
  • NM_138924.3:c.503A>C
  • NP_000147.1:p.Tyr168Ser
  • NP_620279.1:p.Tyr168Ser
  • NC_000019.9:g.1398982T>G
  • NM_000156.4:c.503A>C
  • NM_000156.5:c.503A>C
Protein change:
Y168S
Links:
dbSNP: rs1131691644
NCBI 1000 Genomes Browser:
rs1131691644
Molecular consequence:
  • NM_000156.6:c.503A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_138924.3:c.503A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000582547GeneDxcriteria provided, single submitter
Pathogenic
(Oct 13, 2015)
germlineclinical testing

Citation Link,

SCV000883935ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Dec 5, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000582547.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Y168S pathogenic variant in the GAMT gene has been previously reported in the homozygous state in an individual with phenotypic and biochemical evidence of GAMT deficiency (Bodamer et al., 2009). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This semi-conservative substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (C169R/Y, L166P) have been reported in the Human Gene Mutation Database in association with GAMT deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, Y168S is considered a pathogenic variant.

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

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000883935.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 27, 2021

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