NM_001258392.3(CLPB):c.748C>G (p.Arg250Gly) AND 3-methylglutaconic aciduria, type VIIB

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000694608.6

Allele description

NM_001258392.3(CLPB):c.748C>G (p.Arg250Gly)

Gene:

CLPB:ClpB family mitochondrial disaggregase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001258392.3(CLPB):c.748C>G (p.Arg250Gly)

HGVS:

NC_000011.10:g.72358907G>C
NG_042130.2:g.80778C>G
NM_001258392.3:c.748C>GMANE SELECT
NM_001258393.3:c.661C>G
NM_001258394.3:c.703C>G
NM_030813.6:c.838C>G
NP_001245321.1:p.Arg250Gly
NP_001245322.1:p.Arg221Gly
NP_001245323.1:p.Arg235Gly
NP_110440.1:p.Arg280Gly
LRG_1338t1:c.748C>G
LRG_1338:g.80778C>G
LRG_1338p1:p.Arg250Gly
NC_000011.9:g.72069951G>C
NM_030813.5:c.838C>G

Protein change:

R221G

Links:

dbSNP: rs146762466

NCBI 1000 Genomes Browser:

rs146762466

Molecular consequence:

NM_001258392.3:c.748C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258393.3:c.661C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258394.3:c.703C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_030813.6:c.838C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: 3-methylglutaconic aciduria, type VIIB (MGCA7B)
Synonyms:: 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia
Identifiers:: MONDO: MONDO:0014561; MedGen: C5676893; Orphanet: 445038; OMIM: 616271

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000823060	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	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

SCV000823060

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

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

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000823060.6

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

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 280 of the CLPB protein (p.Arg280Gly). This variant is present in population databases (rs146762466, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CLPB-related conditions. ClinVar contains an entry for this variant (Variation ID: 573047). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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

Last Updated: Feb 20, 2024

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