NM_052845.4(MMAB):c.349-1G>C AND Methylmalonic aciduria, cblB type

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 12, 2023
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:: RCV000202577.5

Allele description [Variation Report for NM_052845.4(MMAB):c.349-1G>C]

NM_052845.4(MMAB):c.349-1G>C

Gene:

MMAB:metabolism of cobalamin associated B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_052845.4(MMAB):c.349-1G>C

HGVS:

NC_000012.12:g.109561853C>G
NG_007096.1:g.16645G>C
NG_126524.1:g.406C>G
NM_052845.4:c.349-1G>CMANE SELECT
NC_000012.11:g.109999658C>G
NM_052845.3:c.349_354delATCCAG

Note:

A splice site mutation in the exon 5 acceptor site results in the in-frame deletion of the first two codons of exon 5 of gene MMAB (PMID 20556797).

Nucleotide change:

IVS4AS, G-C, -1

Links:

OMIM: 607568.0007; dbSNP: rs864309510

NCBI 1000 Genomes Browser:

rs864309510

Molecular consequence:

NM_052845.4:c.349-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Methylmalonic aciduria, cblB type (MACB)
Synonyms:: METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblB TYPE; Methylmalonic acidemia cblB type; Vitamin B12-responsive methylmalonic acidemia type cblB
Identifiers:: MONDO: MONDO:0009614; MedGen: C1855102; Orphanet: 28; Orphanet: 79311; OMIM: 251110

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000257521	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000799634	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 3, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20556797, 20549364 Citation Link,
SCV004193130	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 12, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000257521

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2010)

germline

literature only

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

SCV000799634

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 3, 2018)

unknown

clinical testing

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

Citation Link,

SCV004193130

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 12, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type.

Jorge-Finnigan A, Aguado C, Sánchez-Alcudia R, Abia D, Richard E, Merinero B, Gámez A, Banerjee R, Desviat LR, Ugarte M, Pérez B.

Hum Mutat. 2010 Sep;31(9):1033-42. doi: 10.1002/humu.21307.

PubMed [citation]

PMID:: 20556797
PMCID:: PMC2932867

The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America.

Pérez B, Angaroni C, Sánchez-Alcudia R, Merinero B, Pérez-Cerdá C, Specola N, Rodríguez-Pombo P, Wajner M, de Kremer RD, Cornejo V, Desviat LR, Ugarte M.

J Inherit Metab Dis. 2010 Oct;33(Suppl 2):S307-14. doi: 10.1007/s10545-010-9116-4. Epub 2010 Jun 15.

PubMed [citation]

PMID:: 20549364

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000257521.3

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

Description

In a patient (P4) with methylmalonic aciduria of the cblB type (251110), Jorge-Finnigan et al. (2010) identified compound heterozygous mutations in the MMAB gene: a G-to-C transversion (c.349-1G-C, NM_052845.3) in intron 4, resulting in a splice site mutation and in-frame deletion of the first 6 nucleotides of exon 5 (Ile117_Gln118del), and a c.290G-A transition (607568.0008) in the last nucleotide of exon 3, resulting in the skipping of exon 3 (Gly66fs). The splicing defects were confirmed in patient fibroblasts and minigene assays. The patient had neonatal onset of the disorder, but was asymptomatic at age 12 years.

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

From Counsyl, SCV000799634.1

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

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

From Baylor Genetics, SCV004193130.2

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

Last Updated: Oct 8, 2024

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