NM_000282.4(PCCA):c.1189G>T (p.Glu397Ter) AND Propionic acidemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001383530.5

Allele description [Variation Report for NM_000282.4(PCCA):c.1189G>T (p.Glu397Ter)]

NM_000282.4(PCCA):c.1189G>T (p.Glu397Ter)

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.1189G>T (p.Glu397Ter)

HGVS:

NC_000013.11:g.100301583G>T
NG_008768.1:g.217501G>T
NM_000282.4:c.1189G>TMANE SELECT
NM_001127692.3:c.1111G>T
NM_001178004.2:c.1189G>T
NM_001352605.2:c.1189G>T
NM_001352606.2:c.1066-1341G>T
NM_001352607.2:c.1111G>T
NM_001352608.2:c.988-1341G>T
NM_001352609.2:c.1189G>T
NM_001352610.2:c.244G>T
NM_001352611.2:c.244G>T
NM_001352612.2:c.121-1341G>T
NP_000273.2:p.Glu397Ter
NP_001121164.1:p.Glu371Ter
NP_001171475.1:p.Glu397Ter
NP_001339534.1:p.Glu397Ter
NP_001339536.1:p.Glu371Ter
NP_001339538.1:p.Glu397Ter
NP_001339539.1:p.Glu82Ter
NP_001339540.1:p.Glu82Ter
NC_000013.10:g.100953837G>T
NR_148027.2:n.1217G>T
NR_148028.2:n.1217G>T
NR_148029.2:n.1139G>T
NR_148030.2:n.1217G>T
NR_148031.2:n.1217G>T

Protein change:

E371*

Links:

dbSNP: rs1295357399

NCBI 1000 Genomes Browser:

rs1295357399

Molecular consequence:

NM_001352606.2:c.1066-1341G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001352608.2:c.988-1341G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001352612.2:c.121-1341G>T - intron variant - [Sequence Ontology: SO:0001627]
NR_148027.2:n.1217G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148028.2:n.1217G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148029.2:n.1139G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148030.2:n.1217G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148031.2:n.1217G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000282.4:c.1189G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127692.3:c.1111G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178004.2:c.1189G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352605.2:c.1189G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352607.2:c.1111G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352609.2:c.1189G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352610.2:c.244G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352611.2:c.244G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Propionic acidemia (PROP)
Synonyms:: Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia
Identifiers:: MONDO: MONDO:0011628; MedGen: C0268579; Orphanet: 35; OMIM: 606054; Human Phenotype Ontology: HP:0003571

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001582681	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15464417, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582681

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Propionic acidemia: mutation update and functional and structural effects of the variant alleles.

Desviat LR, Pérez B, Pérez-Cerdá C, Rodríguez-Pombo P, Clavero S, Ugarte M.

Mol Genet Metab. 2004 Sep-Oct;83(1-2):28-37. Review.

PubMed [citation]

PMID:: 15464417

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582681.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1071149). This variant has not been reported in the literature in individuals affected with PCCA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu397*) in the PCCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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