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NM_018368.4(LMBRD1):c.763-2A>C AND Methylmalonic aciduria and homocystinuria type cblF

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 30, 2023
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:
RCV003838357.1

Allele description [Variation Report for NM_018368.4(LMBRD1):c.763-2A>C]

NM_018368.4(LMBRD1):c.763-2A>C

Gene:
LMBRD1:LMBR1 domain containing 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q13
Genomic location:
Preferred name:
NM_018368.4(LMBRD1):c.763-2A>C
HGVS:
  • NC_000006.12:g.69713799T>G
  • NG_016012.2:g.157818A>C
  • NM_001363722.2:c.544-2A>C
  • NM_001367271.1:c.544-2A>C
  • NM_001367272.1:c.544-2A>C
  • NM_018368.4:c.763-2A>CMANE SELECT
  • LRG_1310t1:c.763-2A>C
  • LRG_1310:g.157818A>C
  • NC_000006.11:g.70423691T>G
Molecular consequence:
  • NM_001363722.2:c.544-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001367271.1:c.544-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001367272.1:c.544-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_018368.4:c.763-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Methylmalonic aciduria and homocystinuria type cblF
Synonyms:
COBALAMIN F DISEASE; COBALAMIN, DEFECT IN LYSOSOMAL RELEASE OF; METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblF TYPE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010183; MedGen: C1848578; Orphanet: 79284; OMIM: 277380

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004634371Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(May 30, 2023) 		germlineclinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism.

Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P.

Nat Genet. 2009 Feb;41(2):234-9. doi: 10.1038/ng.294. Epub 2009 Jan 11.

PubMed [citation]
PMID:
19136951
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004634371.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with LMBRD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 8 of the LMBRD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LMBRD1 are known to be pathogenic (PMID: 19136951, 21303734).

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

Last Updated: Mar 5, 2024