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NM_015506.3(MMACHC):c.48_49del (p.Cys17fs) AND Cobalamin C disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 26, 2020
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:
RCV001390500.5

Allele description [Variation Report for NM_015506.3(MMACHC):c.48_49del (p.Cys17fs)]

NM_015506.3(MMACHC):c.48_49del (p.Cys17fs)

Gene:
MMACHC:metabolism of cobalamin associated C [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_015506.3(MMACHC):c.48_49del (p.Cys17fs)
HGVS:
  • NC_000001.11:g.45500380_45500381del
  • NG_013378.1:g.5197_5198del
  • NM_001330540.2:c.-175_-174del
  • NM_015506.3:c.48_49delMANE SELECT
  • NP_056321.2:p.Cys17fs
  • NC_000001.10:g.45966051_45966052del
  • NC_000001.10:g.45966052_45966053del
Protein change:
C17fs
Links:
dbSNP: rs765960386
NCBI 1000 Genomes Browser:
rs765960386
Molecular consequence:
  • NM_001330540.2:c.-175_-174del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_015506.3:c.48_49del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Cobalamin C disease
Synonyms:
Cobalamin-C methylmalonic acidemia and homocystinuria; Methylmalonic acidemia and homocystinuria cblC type; Methylmalonic aciduria and homocystinuria, Vitamin B12-responsive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010184; MedGen: C1848561; Orphanet: 26; Orphanet: 79282; OMIM: 277400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001592240Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 26, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS.

Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27. Erratum in: Nat Genet. 2006 Aug;38(8):957.

PubMed [citation]
PMID:
16311595

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, SCV001592240.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MMACHC are known to be pathogenic (PMID: 16311595). This variant has not been reported in the literature in individuals with MMACHC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Cys17Serfs*16) in the MMACHC gene. It is expected to result in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024