NM_000282.4(PCCA):c.1423A>G (p.Ile475Val) AND Propionic acidemia

Clinical significance:Benign/Likely benign (Last evaluated: Dec 5, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
6 submissions [Details]
Record status:
current
Accession:
RCV000313421.11

Allele description [Variation Report for NM_000282.4(PCCA):c.1423A>G (p.Ile475Val)]

NM_000282.4(PCCA):c.1423A>G (p.Ile475Val)

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.1423A>G (p.Ile475Val)
HGVS:
  • NC_000013.11:g.100309902A>G
  • NG_008768.1:g.225820A>G
  • NM_000282.4:c.1423A>GMANE SELECT
  • NM_001127692.2:c.1345A>G
  • NM_001178004.1:c.1423A>G
  • NM_001352605.2:c.1423A>G
  • NM_001352606.2:c.1279A>G
  • NM_001352607.2:c.1345A>G
  • NM_001352608.2:c.1201A>G
  • NM_001352609.2:c.1423A>G
  • NM_001352610.2:c.478A>G
  • NM_001352611.2:c.478A>G
  • NM_001352612.2:c.334A>G
  • NP_000273.2:p.Ile475Val
  • NP_000273.2:p.Ile475Val
  • NP_000273.2:p.Ile475Val
  • NP_001121164.1:p.Ile449Val
  • NP_001171475.1:p.Ile475Val
  • NP_001339534.1:p.Ile475Val
  • NP_001339535.1:p.Ile427Val
  • NP_001339536.1:p.Ile449Val
  • NP_001339537.1:p.Ile401Val
  • NP_001339538.1:p.Ile475Val
  • NP_001339539.1:p.Ile160Val
  • NP_001339540.1:p.Ile160Val
  • NP_001339541.1:p.Ile112Val
  • NC_000013.10:g.100962156A>G
  • NM_000282.3:c.1423A>G
  • NR_148027.2:n.1535A>G
  • NR_148028.2:n.1535A>G
  • NR_148029.2:n.1457A>G
  • NR_148030.2:n.1535A>G
  • NR_148031.2:n.1451A>G
  • P05165:p.Ile475Val
Protein change:
I112V
Links:
UniProtKB: P05165#VAR_009098; dbSNP: rs35719359
NCBI 1000 Genomes Browser:
rs35719359
Molecular consequence:
  • NM_000282.4:c.1423A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127692.2:c.1345A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178004.1:c.1423A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352605.2:c.1423A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352606.2:c.1279A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352607.2:c.1345A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352608.2:c.1201A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352609.2:c.1423A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352610.2:c.478A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352611.2:c.478A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352612.2:c.334A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148027.2:n.1535A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148028.2:n.1535A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148029.2:n.1457A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148030.2:n.1535A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148031.2:n.1451A>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
SCV000382015Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Mar 6, 2018)
germlineclinical testing

Citation Link,

SCV000631898Invitaecriteria provided, single submitter
Benign
(Dec 5, 2020)
germlineclinical testing

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

SCV000733195Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensusno assertion criteria providedBenigngermlineclinical testing

SCV000744069Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensuscriteria provided, single submitter
Likely benign
(Oct 9, 2014)
germlineclinical testing

Citation Link,

SCV001159024ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Benign
(Jul 4, 2020)
germlineclinical testing

Citation Link,

SCV001455848Natera, Inc.no assertion criteria providedBenign
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

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

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000382015.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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

From Invitae, SCV000631898.3

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733195.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000744069.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001159024.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001455848.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 12, 2021

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