NM_000920.3(PC):c.796T>G (p.Ser266Ala) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000431389.2

Allele description [Variation Report for NM_000920.3(PC):c.796T>G (p.Ser266Ala)]

NM_000920.3(PC):c.796T>G (p.Ser266Ala)

Gene:
PC:pyruvate carboxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.2
Genomic location:
Preferred name:
NM_000920.3(PC):c.796T>G (p.Ser266Ala)
HGVS:
  • NC_000011.10:g.66870409A>C
  • NG_008319.1:g.92968T>G
  • NM_000920.3:c.796T>G
  • NM_001040716.1:c.796T>G
  • NP_000911.2:p.Ser266Ala
  • NP_001035806.1:p.Ser266Ala
  • NC_000011.9:g.66637880A>C
Protein change:
S266A
Links:
dbSNP: rs113994142
NCBI 1000 Genomes Browser:
rs113994142
Molecular consequence:
  • NM_001040716.1:c.796T>G - 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
SCV000520993GeneDxcriteria provided, single submitter
Likely pathogenic
(Aug 7, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000520993.4

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

Description

The S266A variant in the PC gene has been reported previously in an individual with pyruvate carboxylase deficiency who appeared to be compound heterozygous for S266A and a protein truncating variant, however parental testing was not performed to confirm these variants were on opposite alleles (Wang et al., 2008). The S266A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S266A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The S266A variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.

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

Last Updated: Apr 17, 2019

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