NM_000532.5(PCCB):c.774C>G (p.His258Gln) AND not specified

Clinical significance:Likely benign (Last evaluated: Feb 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001192545.1

Allele description [Variation Report for NM_000532.5(PCCB):c.774C>G (p.His258Gln)]

NM_000532.5(PCCB):c.774C>G (p.His258Gln)

Gene:
PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q22.3
Genomic location:
Preferred name:
NM_000532.5(PCCB):c.774C>G (p.His258Gln)
HGVS:
  • NC_000003.12:g.136297962C>G
  • NG_008939.1:g.52638C>G
  • NM_000532.5:c.774C>GMANE SELECT
  • NM_001178014.1:c.834C>G
  • NP_000523.2:p.His258Gln
  • NP_001171485.1:p.His278Gln
  • NC_000003.11:g.136016804C>G
  • NM_000532.4:c.774C>G
Protein change:
H258Q
Links:
dbSNP: rs141615209
NCBI 1000 Genomes Browser:
rs141615209
Molecular consequence:
  • NM_000532.5:c.774C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178014.1:c.834C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001360758Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Feb 7, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360758.1

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

Description

Variant summary: PCCB c.774C>G (p.His258Gln) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, N-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 277206 control chromosomes, predominantly at a frequency of 0.0049 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCCB causing Propionic Acidemia phenotype (0.0025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.774C>G in individuals affected with Propionic Acidemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Sep 23, 2021

Support Center