NM_000282.4(PCCA):c.1426C>T (p.Arg476Ter) AND Propionic acidemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Dec 27, 2018)

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:
RCV000236395.2

Allele description [Variation Report for NM_000282.4(PCCA):c.1426C>T (p.Arg476Ter)]

NM_000282.4(PCCA):c.1426C>T (p.Arg476Ter)

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.1426C>T (p.Arg476Ter)
HGVS:
  • NC_000013.11:g.100309905C>T
  • NG_008768.1:g.225823C>T
  • NM_000282.4:c.1426C>TMANE SELECT
  • NM_001127692.2:c.1348C>T
  • NM_001178004.1:c.1426C>T
  • NM_001352605.2:c.1426C>T
  • NM_001352606.2:c.1282C>T
  • NM_001352607.2:c.1348C>T
  • NM_001352608.2:c.1204C>T
  • NM_001352609.2:c.1426C>T
  • NM_001352610.2:c.481C>T
  • NM_001352611.2:c.481C>T
  • NM_001352612.2:c.337C>T
  • NP_000273.2:p.Arg476Ter
  • NP_001121164.1:p.Arg450Ter
  • NP_001171475.1:p.Arg476Ter
  • NP_001339534.1:p.Arg476Ter
  • NP_001339535.1:p.Arg428Ter
  • NP_001339536.1:p.Arg450Ter
  • NP_001339537.1:p.Arg402Ter
  • NP_001339538.1:p.Arg476Ter
  • NP_001339539.1:p.Arg161Ter
  • NP_001339540.1:p.Arg161Ter
  • NP_001339541.1:p.Arg113Ter
  • NC_000013.10:g.100962159C>T
  • NM_000282.3:c.1426C>T
  • NR_148027.2:n.1538C>T
  • NR_148028.2:n.1538C>T
  • NR_148029.2:n.1460C>T
  • NR_148030.2:n.1538C>T
  • NR_148031.2:n.1454C>T
Protein change:
R113*
Links:
dbSNP: rs768703749
NCBI 1000 Genomes Browser:
rs768703749
Molecular consequence:
  • NR_148027.2:n.1538C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148028.2:n.1538C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148029.2:n.1460C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148030.2:n.1538C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148031.2:n.1454C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000282.4:c.1426C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127692.2:c.1348C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178004.1:c.1426C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352605.2:c.1426C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352606.2:c.1282C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352607.2:c.1348C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352608.2:c.1204C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352609.2:c.1426C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352610.2:c.481C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352611.2:c.481C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352612.2:c.337C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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
SCV000256855Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital - ORGANIC ACIDURIAScriteria provided, single submitter
Pathogenic
(Jan 1, 2012)
germlineresearch

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

SCV000800257Counsylcriteria provided, single submitter
Likely pathogenic
(May 29, 2018)
unknownclinical testing

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

Citation Link,

SCV000936965Invitaecriteria provided, single submitter
Pathogenic
(Dec 27, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Description

Nonsense mutation

SCV000256855

Summary from all submissions

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

Citations

PubMed

Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes.

Gupta D, Bijarnia-Mahay S, Kohli S, Saxena R, Puri RD, Shigematsu Y, Yamaguchi S, Sakamoto O, Gupta N, Kabra M, Thakur S, Deb R, Verma IC.

Genet Test Mol Biomarkers. 2016 Jul;20(7):373-82. doi: 10.1089/gtmb.2016.0017. Epub 2016 May 26.

PubMed [citation]
PMID:
27227689

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

Details of each submission

From Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital - ORGANIC ACIDURIAS, SCV000256855.1

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

From Counsyl, SCV000800257.1

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

From Invitae, SCV000936965.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Arg476*) in the PCCA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs768703749, ExAC 0.02%). This variant has been observed in to be homozygous in an individual  affected with propionic acidemia (PMID: 27227689). ClinVar contains an entry for this variant (Variation ID: 218264). Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). 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

Support Center