NM_032601.4(MCEE):c.375_378+4del AND Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 27, 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:: RCV003499961.2

Allele description [Variation Report for NM_032601.4(MCEE):c.375_378+4del]

NM_032601.4(MCEE):c.375_378+4del

Gene:

MCEE:methylmalonyl-CoA epimerase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p13.3

Genomic location:

Preferred name:

NM_032601.4(MCEE):c.375_378+4del

HGVS:

NC_000002.12:g.71124204_71124211del
NG_008977.1:g.11056_11063del
NM_032601.4:c.375_378+4delMANE SELECT
NC_000002.11:g.71351332_71351339del
NC_000002.11:g.71351334_71351341del

Molecular consequence:

NM_032601.4:c.375_378+4del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency
Synonyms:: METHYLMALONYL-CoA RACEMASE DEFICIENCY; METHYLMALONIC ACIDURIA III; Methylmalonyl-CoA epimerase deficiency
Identifiers:: MONDO: MONDO:0009615; MedGen: C1855100; OMIM: 251120

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004294299	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 16697227, 16752391, 30682498, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294299

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 27, 2023)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria.

Dobson CM, Gradinger A, Longo N, Wu X, Leclerc D, Lerner-Ellis J, Lemieux M, Belair C, Watkins D, Rosenblatt DS, Gravel RA.

Mol Genet Metab. 2006 Aug;88(4):327-33. Epub 2006 May 11.

PubMed [citation]

PMID:: 16697227

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004294299.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with MCEE-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 2 (c.375_378+4del) of the MCEE gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MCEE are known to be pathogenic (PMID: 16697227, 16752391, 30682498).

#	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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