NM_000282.4(PCCA):c.2002G>A (p.Gly668Arg) AND Propionic acidemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Apr 28, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000235940.3

Allele description [Variation Report for NM_000282.4(PCCA):c.2002G>A (p.Gly668Arg)]

NM_000282.4(PCCA):c.2002G>A (p.Gly668Arg)

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.2002G>A (p.Gly668Arg)
HGVS:
  • NC_000013.11:g.100515529G>A
  • NG_008768.1:g.431447G>A
  • NM_000282.4:c.2002G>AMANE SELECT
  • NM_001127692.2:c.1924G>A
  • NM_001178004.1:c.1900-12146G>A
  • NM_001352605.2:c.1948G>A
  • NM_001352606.2:c.1858G>A
  • NM_001352607.2:c.1822-12146G>A
  • NM_001352608.2:c.1780G>A
  • NM_001352610.2:c.1057G>A
  • NM_001352611.2:c.1003G>A
  • NM_001352612.2:c.913G>A
  • NP_000273.2:p.Gly668Arg
  • NP_001121164.1:p.Gly642Arg
  • NP_001339534.1:p.Gly650Arg
  • NP_001339535.1:p.Gly620Arg
  • NP_001339537.1:p.Gly594Arg
  • NP_001339539.1:p.Gly353Arg
  • NP_001339540.1:p.Gly335Arg
  • NP_001339541.1:p.Gly305Arg
  • NC_000013.10:g.101167783G>A
  • NM_000282.3:c.2002G>A
  • NR_148028.2:n.2011G>A
  • NR_148029.2:n.1933G>A
  • NR_148030.2:n.2114G>A
  • NR_148031.2:n.1927G>A
  • P05165:p.Gly668Arg
Protein change:
G305R
Links:
UniProtKB: P05165#VAR_009101; dbSNP: rs771438170
NCBI 1000 Genomes Browser:
rs771438170
Molecular consequence:
  • NM_001178004.1:c.1900-12146G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001352607.2:c.1822-12146G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000282.4:c.2002G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127692.2:c.1924G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352605.2:c.1948G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352606.2:c.1858G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352608.2:c.1780G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352610.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352611.2:c.1003G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352612.2:c.913G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148028.2:n.2011G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148029.2:n.1933G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148030.2:n.2114G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148031.2:n.1927G>A - 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
SCV000256857Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital - ORGANIC ACIDURIAScriteria provided, single submitter
Pathogenic
(Jan 1, 2014)
germlineresearch

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

SCV000791909Counsylcriteria provided, single submitter
Likely pathogenic
(May 31, 2017)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV001398286Invitaecriteria provided, single submitter
Pathogenic
(Apr 28, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Description

Missense mutation

SCV000256857

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.

Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, Tong L.

Nature. 2010 Aug 19;466(7309):1001-5. doi: 10.1038/nature09302.

PubMed [citation]
PMID:
20725044
PMCID:
PMC2925307

Novel Heterozygous PCCA Mutations with Fatal Outcome in Propionic Acidemia.

Yang B, Tang W.

Indian Pediatr. 2018 Jun 15;55(6):529-530. No abstract available.

PubMed [citation]
PMID:
29978829
See all PubMed Citations (7)

Details of each submission

From Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital - ORGANIC ACIDURIAS, SCV000256857.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Counsyl, SCV000791909.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001398286.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with arginine at codon 668 of the PCCA protein (p.Gly668Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs771438170, ExAC 0.009%). This variant has been observed in individuals affected with propionic acidemia (PMID: 10329019, 29978829, 27227689, 19099776). ClinVar contains an entry for this variant (Variation ID: 218266). This variant has been reported to affect PCCA protein function (PMID: 10329019, 12385775). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jun 22, 2021

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