NM_032601.4(MCEE):c.178A>C (p.Lys60Gln) AND Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jan 31, 2024
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:: RCV000203363.18

Allele description [Variation Report for NM_032601.4(MCEE):c.178A>C (p.Lys60Gln)]

NM_032601.4(MCEE):c.178A>C (p.Lys60Gln)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.3

Genomic location:

Preferred name:

NM_032601.4(MCEE):c.178A>C (p.Lys60Gln)

Other names:

p.K60Q:AAG>CAG

HGVS:

NC_000002.12:g.71124406T>G
NG_008977.1:g.10859A>C
NM_032601.4:c.178A>CMANE SELECT
NP_115990.3:p.Lys60Gln
NC_000002.11:g.71351536T>G
NM_032601.3:c.178A>C

Protein change:

K60Q

Links:

dbSNP: rs147401037

NCBI 1000 Genomes Browser:

rs147401037

Molecular consequence:

NM_032601.4:c.178A>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000258536	GeneReviews	no classification provided	not provided	germline	literature only
SCV001115025	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001435154	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	research	PubMed (2) [See all records that cite these PMIDs] 17823972, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000258536

GeneReviews

no classification provided

not provided

germline

literature only

SCV001115025

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 31, 2024)

germline

clinical testing

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

SCV001435154

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign

germline

research

PubMed (2)
[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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only, research

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

Atypical methylmalonic aciduria: frequency of mutations in the methylmalonyl CoA epimerase gene (MCEE).

Gradinger AB, Bélair C, Worgan LC, Li CD, Lavallée J, Roquis D, Watkins D, Rosenblatt DS.

Hum Mutat. 2007 Oct;28(10):1045.

PubMed [citation]

PMID:: 17823972

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000258536.2

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

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

From Invitae, SCV001115025.5

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001435154.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

The homozygous p.Lys60Gln variant in MCEE has been identified in an individual with methylmalonic aciduria (PMID: 17823972), but has also been identified in >1% of South Asian chromosomes and 8 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal recessive methylmalonic aciduria.

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

Last Updated: Sep 16, 2024

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