U.S. flag

An official website of the United States government

NM_000532.5(PCCB):c.472C>G (p.Leu158Val) AND Propionic acidemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 27, 2021
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:
RCV002003198.4

Allele description

NM_000532.5(PCCB):c.472C>G (p.Leu158Val)

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.472C>G (p.Leu158Val)
HGVS:
  • NC_000003.12:g.136261994C>G
  • NG_008939.1:g.16670C>G
  • NM_000532.5:c.472C>GMANE SELECT
  • NM_001178014.2:c.532C>G
  • NP_000523.2:p.Leu158Val
  • NP_001171485.1:p.Leu178Val
  • NC_000003.11:g.135980836C>G
Protein change:
L158V
Links:
dbSNP: rs2108146685
NCBI 1000 Genomes Browser:
rs2108146685
Molecular consequence:
  • NM_000532.5:c.472C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178014.2:c.532C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Propionic acidemia (PROP)
Synonyms:
Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia
Identifiers:
MONDO: MONDO:0011628; MedGen: C0268579; Orphanet: 35; OMIM: 606054; Human Phenotype Ontology: HP:0003571

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002276901Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 27, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002276901.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with valine at codon 158 of the PCCB protein (p.Leu158Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PCCB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 24, 2023