NM_000532.5(PCCB):c.11_28dup (p.Ala4_Ala9dup) AND Propionic acidemia

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Aug 10, 2022
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:: RCV000665243.5

Allele description [Variation Report for NM_000532.5(PCCB):c.11_28dup (p.Ala4_Ala9dup)]

NM_000532.5(PCCB):c.11_28dup (p.Ala4_Ala9dup)

Gene:

PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3q22.3

Genomic location:

Preferred name:

NM_000532.5(PCCB):c.11_28dup (p.Ala4_Ala9dup)

HGVS:

NC_000003.12:g.136250386_136250403dup
NG_008939.1:g.5062_5079dup
NM_000532.5:c.11_28dupMANE SELECT
NM_001178014.2:c.11_28dup
NP_000523.2:p.Ala4_Ala9dup
NP_001171485.1:p.Ala4_Ala9dup
NC_000003.11:g.135969218_135969219insTGGCGGCGGCATTACGGG
NC_000003.11:g.135969228_135969245dup
NM_000532.4:c.11_28dup
NM_001178014.1:c.11_28dupCATTACGGGTGGCGGCGG

Links:

dbSNP: rs777359703

NCBI 1000 Genomes Browser:

rs777359703

Molecular consequence:

NM_000532.5:c.11_28dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001178014.2:c.11_28dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_000532.5:c.11_28dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001178014.2:c.11_28dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]

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
SCV000789332	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jan 25, 2017)	unknown	clinical testing	Citation Link,
SCV000840318	GenomeConnect, ClinGen	no classification provided	not provided	maternal	phenotyping only
SCV000948169	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002081457	Natera, Inc.	no assertion criteria provided	Uncertain significance (Oct 28, 2019)	germline	clinical testing

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
not provided	maternal	unknown	not provided	not provided	not provided	not provided	not provided	phenotyping only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Counsyl, SCV000789332.2

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

#	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

From GenomeConnect, ClinGen, SCV000840318.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From Invitae, SCV000948169.3

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

Description

This variant, c.11_28dup, results in the insertion of 6 amino acid(s) of the PCCB protein (p.Ala4_Ala9dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs777359703, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PCCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 550487). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Natera, Inc., SCV002081457.2

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

#	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 3, 2023

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