NM_000282.4(PCCA):c.782A>G (p.Glu261Gly) AND Propionic acidemia

Clinical significance:Uncertain significance (Last evaluated: Aug 16, 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:
RCV000538185.2

Allele description [Variation Report for NM_000282.4(PCCA):c.782A>G (p.Glu261Gly)]

NM_000282.4(PCCA):c.782A>G (p.Glu261Gly)

Gene:
PCCA:propionyl-CoA carboxylase subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q32.3
Genomic location:
Preferred name:
NM_000282.4(PCCA):c.782A>G (p.Glu261Gly)
HGVS:
  • NC_000013.11:g.100262794A>G
  • NG_008768.1:g.178712A>G
  • NM_000282.4:c.782A>GMANE SELECT
  • NM_001127692.2:c.704A>G
  • NM_001178004.1:c.782A>G
  • NM_001352605.2:c.782A>G
  • NM_001352606.2:c.782A>G
  • NM_001352607.2:c.704A>G
  • NM_001352608.2:c.704A>G
  • NM_001352609.2:c.782A>G
  • NM_001352610.2:c.-164A>G
  • NM_001352611.2:c.-164A>G
  • NM_001352612.2:c.-164A>G
  • NP_000273.2:p.Glu261Gly
  • NP_001121164.1:p.Glu235Gly
  • NP_001171475.1:p.Glu261Gly
  • NP_001339534.1:p.Glu261Gly
  • NP_001339535.1:p.Glu261Gly
  • NP_001339536.1:p.Glu235Gly
  • NP_001339537.1:p.Glu235Gly
  • NP_001339538.1:p.Glu261Gly
  • NC_000013.10:g.100915048A>G
  • NM_000282.3:c.782A>G
  • NR_148027.2:n.810A>G
  • NR_148028.2:n.810A>G
  • NR_148029.2:n.732A>G
  • NR_148030.2:n.810A>G
  • NR_148031.2:n.810A>G
Protein change:
E235G
Links:
dbSNP: rs1169861687
NCBI 1000 Genomes Browser:
rs1169861687
Molecular consequence:
  • NM_001352610.2:c.-164A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001352611.2:c.-164A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001352612.2:c.-164A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000282.4:c.782A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127692.2:c.704A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178004.1:c.782A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352605.2:c.782A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352606.2:c.782A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352607.2:c.704A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352608.2:c.704A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352609.2:c.782A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148027.2:n.810A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148028.2:n.810A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148029.2:n.732A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148030.2:n.810A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148031.2:n.810A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Propionic acidemia (PROP)
Synonyms:
Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011628; MedGen: C0268579; Orphanet: 35; OMIM: 606054; Human Phenotype Ontology: HP:0003353

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000631908Invitaecriteria provided, single submitter
Uncertain significance
(Aug 16, 2017)
germlineclinical testing

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

SCV000793220Counsylcriteria provided, single submitter
Uncertain significance
(Aug 4, 2017)
unknownclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

New splicing mutations in propionic acidemia.

Desviat LR, Clavero S, Perez-Cerdá C, Navarrete R, Ugarte M, Perez B.

J Hum Genet. 2006;51(11):992-997. doi: 10.1007/s10038-006-0068-3. Epub 2006 Oct 19.

PubMed [citation]
PMID:
17051315

Details of each submission

From Invitae, SCV000631908.1

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

Description

This sequence change replaces glutamic acid with glycine at codon 261 of the PCCA protein (p.Glu261Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with another PCCA variant in individuals affected with propionic acidaemia (PMID: 17051315, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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

From Counsyl, SCV000793220.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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