NM_000282.4(PCCA):c.1312G>T (p.Gly438Ter) AND Propionic acidemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 30, 2023
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:: RCV001386768.4

Allele description [Variation Report for NM_000282.4(PCCA):c.1312G>T (p.Gly438Ter)]

NM_000282.4(PCCA):c.1312G>T (p.Gly438Ter)

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.1312G>T (p.Gly438Ter)

HGVS:

NC_000013.11:g.100307219G>T
NG_008768.1:g.223137G>T
NM_000282.4:c.1312G>TMANE SELECT
NM_001127692.3:c.1234G>T
NM_001178004.2:c.1312G>T
NM_001352605.2:c.1312G>T
NM_001352606.2:c.1168G>T
NM_001352607.2:c.1234G>T
NM_001352608.2:c.1090G>T
NM_001352609.2:c.1312G>T
NM_001352610.2:c.367G>T
NM_001352611.2:c.367G>T
NM_001352612.2:c.223G>T
NP_000273.2:p.Gly438Ter
NP_001121164.1:p.Gly412Ter
NP_001171475.1:p.Gly438Ter
NP_001339534.1:p.Gly438Ter
NP_001339535.1:p.Gly390Ter
NP_001339536.1:p.Gly412Ter
NP_001339537.1:p.Gly364Ter
NP_001339538.1:p.Gly438Ter
NP_001339539.1:p.Gly123Ter
NP_001339540.1:p.Gly123Ter
NP_001339541.1:p.Gly75Ter
NC_000013.10:g.100959473G>T
NR_148027.2:n.1424G>T
NR_148028.2:n.1424G>T
NR_148029.2:n.1346G>T
NR_148030.2:n.1424G>T
NR_148031.2:n.1340G>T

Protein change:

G123*

Links:

dbSNP: rs2152692650

NCBI 1000 Genomes Browser:

rs2152692650

Molecular consequence:

NR_148027.2:n.1424G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148028.2:n.1424G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148029.2:n.1346G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148030.2:n.1424G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148031.2:n.1340G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000282.4:c.1312G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127692.3:c.1234G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178004.2:c.1312G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352605.2:c.1312G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352606.2:c.1168G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352607.2:c.1234G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352608.2:c.1090G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352609.2:c.1312G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352610.2:c.367G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352611.2:c.367G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352612.2:c.223G>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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Chain A, NITRIC OXIDE SYNTHASE, BRAIN
Chain A, NITRIC OXIDE SYNTHASE, BRAIN
gi|635575747|pdb|4CTU|A

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587116	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 30, 2023)	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

SCV001587116

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 30, 2023)

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 Invitae, SCV001587116.4

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

Description

This sequence change creates a premature translational stop signal (p.Gly438*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1073696). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2024

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