NM_015506.3(MMACHC):c.688C>T (p.Arg230Ter) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 8, 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:: RCV003994027.2

Allele description [Variation Report for NM_015506.3(MMACHC):c.688C>T (p.Arg230Ter)]

NM_015506.3(MMACHC):c.688C>T (p.Arg230Ter)

Genes:

LOC129930446:ATAC-STARR-seq lymphoblastoid active region 972 [Gene]
MMACHC:metabolism of cobalamin associated C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_015506.3(MMACHC):c.688C>T (p.Arg230Ter)

HGVS:

NC_000001.11:g.45509054C>T
NG_013378.1:g.13871C>T
NM_001330540.2:c.517C>T
NM_015506.3:c.688C>TMANE SELECT
NP_001317469.1:p.Arg173Ter
NP_056321.2:p.Arg230Ter
NC_000001.10:g.45974726C>T
NM_015506.2:c.688C>T

Protein change:

R173*

Links:

dbSNP: rs201183360

NCBI 1000 Genomes Browser:

rs201183360

Molecular consequence:

NM_001330540.2:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015506.3:c.688C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002570885	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26990548, 31589614 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002570885

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 8, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

NGS-Based Assay for the Identification of Individuals Carrying Recessive Genetic Mutations in Reproductive Medicine.

Abulí A, Boada M, Rodríguez-Santiago B, Coroleu B, Veiga A, Armengol L, Barri PN, Pérez-Jurado LA, Estivill X.

Hum Mutat. 2016 Jun;37(6):516-23. doi: 10.1002/humu.22989. Epub 2016 Apr 15.

PubMed [citation]

PMID:: 26990548

Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.

Capalbo A, Valero RA, Jimenez-Almazan J, Pardo PM, Fabiani M, Jiménez D, Simon C, Rodriguez JM.

PLoS Genet. 2019 Oct;15(10):e1008409. doi: 10.1371/journal.pgen.1008409.

PubMed [citation]

PMID:: 31589614
PMCID:: PMC6797235

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002570885.3

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

Description

Variant summary: MMACHC c.688C>T (p.Arg230X) results in a premature termination codon, predicted to cause a truncation of the encoded protein. No variants (nonsesen/frameshifting/missense/inframe deletions) downstream of this position have been classified as pathogenic. The variant allele was found at a frequency of 6.8e-05 in 249066 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MMACHC causing Methylmalonic Acidemia With Homocystinuria (6.8e-05 vs 0.0032), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.688C>T in individuals affected with Methylmalonic Acidemia With Homocystinuria and no experimental evidence demonstrating its impact on protein function have been reported. However, the variant was reported as a pathogenic/likely pathogenic variant in two large carrier screenings (Abuli_2016, Capalbo_2019). The following publications have been ascertained in the context of this evaluation (PMID: 26990548, 31589614). ClinVar contains an entry for this variant (Variation ID: 488706). Based on the evidence outlined above, the variant was classified as VUS.

#	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: May 25, 2025

ClinVar

Relating variation to medicine