NM_001040716.2(PC):c.1639C>T (p.Arg547Ter) AND Pyruvate carboxylase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 16, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003087326.3

Allele description [Variation Report for NM_001040716.2(PC):c.1639C>T (p.Arg547Ter)]

NM_001040716.2(PC):c.1639C>T (p.Arg547Ter)

Gene:

PC:pyruvate carboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_001040716.2(PC):c.1639C>T (p.Arg547Ter)

HGVS:

NC_000011.10:g.66852625G>A
NG_008319.1:g.110752C>T
NM_000920.4:c.1639C>T
NM_001040716.2:c.1639C>TMANE SELECT
NM_022172.3:c.1639C>T
NP_000911.2:p.Arg547Ter
NP_001035806.1:p.Arg547Ter
NP_071504.2:p.Arg547Ter
NC_000011.9:g.66620096G>A

Protein change:

R547*

Molecular consequence:

NM_000920.4:c.1639C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001040716.2:c.1639C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022172.3:c.1639C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Pyruvate carboxylase deficiency
Synonyms:: ATAXIA WITH LACTIC ACIDOSIS II; PC deficiency; Ataxia with lactic acidosis 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009949; MedGen: C0034341; Orphanet: 3008; OMIM: 266150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003487769	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12112657, 19306334, 28492532
SCV004202816	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 15, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003487769

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 16, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004202816

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 15, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings.

Carbone MA, Applegarth DA, Robinson BH.

Hum Mutat. 2002 Jul;20(1):48-56.

PubMed [citation]

PMID:: 12112657

Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency.

Monnot S, Serre V, Chadefaux-Vekemans B, Aupetit J, Romano S, De Lonlay P, Rival JM, Munnich A, Steffann J, Bonnefont JP.

Hum Mutat. 2009 May;30(5):734-40. doi: 10.1002/humu.20908.

PubMed [citation]

PMID:: 19306334

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003487769.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with PC-related conditions. This sequence change creates a premature translational stop signal (p.Arg547*) in the PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PC are known to be pathogenic (PMID: 12112657, 19306334). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 2172239). 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

From Baylor Genetics, SCV004202816.1

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

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

Last Updated: Feb 28, 2024

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