NM_000532.5(PCCB):c.1379_1385del (p.Ile460fs) AND Propionic acidemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 10, 2020)

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:
RCV000674212.2

Allele description [Variation Report for NM_000532.5(PCCB):c.1379_1385del (p.Ile460fs)]

NM_000532.5(PCCB):c.1379_1385del (p.Ile460fs)

Gene:
PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
3q22.3
Genomic location:
Preferred name:
NM_000532.5(PCCB):c.1379_1385del (p.Ile460fs)
HGVS:
  • NC_000003.12:g.136327713_136327719del
  • NG_008939.1:g.82389_82395del
  • NM_000532.5:c.1379_1385delMANE SELECT
  • NM_001178014.1:c.1439_1445del
  • NP_000523.2:p.Ile460fs
  • NP_001171485.1:p.Ile480fs
  • NC_000003.11:g.136046555_136046561del
  • NM_000532.4:c.1379_1385del7
Protein change:
I460fs
Links:
dbSNP: rs1553784721
NCBI 1000 Genomes Browser:
rs1553784721
Molecular consequence:
  • NM_000532.5:c.1379_1385del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001178014.1:c.1439_1445del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000799512Counsylcriteria provided, single submitter
Likely pathogenic
(Apr 27, 2018)
unknownclinical testing

Citation Link,

SCV001585945Invitaecriteria provided, single submitter
Pathogenic
(Jun 10, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias.

Nizon M, Ottolenghi C, Valayannopoulos V, Arnoux JB, Barbier V, Habarou F, Desguerre I, Boddaert N, Bonnefont JP, Acquaviva C, Benoist JF, Rabier D, Touati G, de Lonlay P.

Orphanet J Rare Dis. 2013 Sep 23;8:148. doi: 10.1186/1750-1172-8-148.

PubMed [citation]
PMID:
24059531
PMCID:
PMC4016503
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000799512.1

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

From Invitae, SCV001585945.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change results in a frameshift in the PCCB gene (p.Ile460Thrfs*89). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acids of the PCCB protein and extend the protein by an additional 8 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PCCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 558001). This variant disrupts the C-terminus of the PCCB protein. Other variant(s) that disrupt this region (p.Arg514*) have been determined to be pathogenic (PMID: 27227689, 11136555, 24059531, 11136555). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Oct 7, 2021

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