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:

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

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

PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000532.5(PCCB):c.774C>G (p.His258Gln)
  • 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:
dbSNP: rs141615209
NCBI 1000 Genomes Browser:
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]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
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


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.

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

Last Updated: Sep 23, 2021

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