NM_001258392.3(CLPB):c.271C>T (p.Leu91Phe) AND 3-methylglutaconic aciduria, type VIIB

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 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:: RCV003752315.3

Allele description [Variation Report for NM_001258392.3(CLPB):c.271C>T (p.Leu91Phe)]

NM_001258392.3(CLPB):c.271C>T (p.Leu91Phe)

Genes:

LOC130006336:ATAC-STARR-seq lymphoblastoid active region 5191 [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.271C>T (p.Leu91Phe)

HGVS:

NC_000011.10:g.72434204G>A
NG_042130.2:g.5481C>T
NG_185781.1:g.152G>A
NM_001258392.3:c.271C>TMANE SELECT
NM_001258393.3:c.271C>T
NM_001258394.3:c.29C>T
NM_030813.6:c.271C>T
NP_001245321.1:p.Leu91Phe
NP_001245322.1:p.Leu91Phe
NP_001245323.1:p.Pro10Leu
NP_110440.1:p.Leu91Phe
LRG_1338t1:c.271C>T
LRG_1338:g.5481C>T
LRG_1338p1:p.Leu91Phe
NC_000011.9:g.72145248G>A

Protein change:

L91F

Molecular consequence:

NM_001258392.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258393.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258394.3:c.29C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_030813.6:c.271C>T - 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
SCV004452683	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 30, 2023)	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

SCV004452683

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 30, 2023)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004452683.1

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

Description

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. 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. This variant has not been reported in the literature in individuals affected with CLPB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 91 of the CLPB protein (p.Leu91Phe).

#	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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