NM_172250.3(MMAA):c.139_140del (p.Leu47fs) AND Methylmalonic aciduria, cblA type

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 6, 2018
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:: RCV000690978.5

Allele description [Variation Report for NM_172250.3(MMAA):c.139_140del (p.Leu47fs)]

NM_172250.3(MMAA):c.139_140del (p.Leu47fs)

Gene:

MMAA:metabolism of cobalamin associated A [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

4q31.21

Genomic location:

Preferred name:

NM_172250.3(MMAA):c.139_140del (p.Leu47fs)

HGVS:

NC_000004.11:g.146560427_146560428del
NC_000004.12:g.145639276CT[1]
NG_007536.2:g.45235CT[1]
NM_001375644.1:c.139_140del
NM_172250.3:c.139_140delMANE SELECT
NP_001362573.1:p.Leu47fs
NP_758454.1:p.Leu47fs
LRG_1301t1:c.139_140del
LRG_1301:g.45235CT[1]
LRG_1301p1:p.Leu47fs
NC_000004.11:g.146560427_146560428del
NC_000004.11:g.146560427_146560428delTC
NC_000004.11:g.146560428CT[1]
NM_172250.2:c.139_140delCT

Protein change:

L47fs

Links:

dbSNP: rs1560795828

NCBI 1000 Genomes Browser:

rs1560795828

Molecular consequence:

NM_001375644.1:c.139_140del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172250.3:c.139_140del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Methylmalonic aciduria, cblA type (MACA)
Synonyms:: Methylmalonic aciduria, vitamin b12-responsive, due to defect in synthesis of adenosylcobalamin, cbla complementation type; MMA cbl A type; Methylmalonic acidemia cblA type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009613; MedGen: C1855109; Orphanet: 28; Orphanet: 79310; OMIM: 251100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000818711	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 6, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15523652, 15781192, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000818711

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 6, 2018)

germline

clinical testing

PubMed (3)
[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

Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism.

Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Doré C, Lepage P, Gravel RA, Rosenblatt DS.

Hum Mutat. 2004 Dec;24(6):509-16. Erratum in: Hum Mutat. 2005 Mar;25(3):317.

PubMed [citation]

PMID:: 15523652

Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.

Martínez MA, Rincón A, Desviat LR, Merinero B, Ugarte M, Pérez B.

Mol Genet Metab. 2005 Apr;84(4):317-25. Epub 2005 Jan 22.

PubMed [citation]

PMID:: 15781192

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000818711.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu47Trpfs*33) in the MMAA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MMAA-related disease. Loss-of-function variants in MMAA are known to be pathogenic (PMID: 15523652, 15781192). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 8, 2024

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