NM_005908.4(MANBA):c.693G>A (p.Trp231Ter) AND Beta-D-mannosidosis

Clinical significance:Pathogenic (Last evaluated: May 25, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000780390.1

Allele description [Variation Report for NM_005908.4(MANBA):c.693G>A (p.Trp231Ter)]

NM_005908.4(MANBA):c.693G>A (p.Trp231Ter)

Gene:
MANBA:mannosidase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q24
Genomic location:
Preferred name:
NM_005908.4(MANBA):c.693G>A (p.Trp231Ter)
HGVS:
  • NC_000004.12:g.102690752C>T
  • NG_012804.1:g.75243G>A
  • NG_012804.2:g.75243G>A
  • NM_005908.4:c.693G>AMANE SELECT
  • NP_005899.3:p.Trp231Ter
  • NC_000004.11:g.103611909C>T
  • NM_005908.3:c.693G>A
Protein change:
W231*
Links:
dbSNP: rs763849774
NCBI 1000 Genomes Browser:
rs763849774
Molecular consequence:
  • NM_005908.4:c.693G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Beta-D-mannosidosis (MANSB)
Synonyms:
Mannosidosis, beta A, lysosomal; Lysosomal beta-mannosidase deficiency; Beta-mannosidase deficiency
Identifiers:
MONDO: MONDO:0009562; MedGen: C4048196; Orphanet: 118; OMIM: 248510

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000917603Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(May 25, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Identification of two novel beta-mannosidosis-associated sequence variants: biochemical analysis of beta-mannosidase (MANBA) missense mutations.

Riise Stensland HMF, Persichetti E, Sorriso C, Hansen GM, Bibi L, Paciotti S, Balducci C, Beccari T.

Mol Genet Metab. 2008 Aug;94(4):476-480. doi: 10.1016/j.ymgme.2008.04.010. Epub 2008 Jun 18.

PubMed [citation]
PMID:
18565776

A comparative structural bioinformatics analysis of inherited mutations in β-D-Mannosidase across multiple species reveals a genotype-phenotype correlation.

Huynh T, Khan JM, Ranganathan S.

BMC Genomics. 2011 Nov 30;12 Suppl 3:S22. doi: 10.1186/1471-2164-12-S3-S22. Epub 2011 Nov 30.

PubMed [citation]
PMID:
22369051
PMCID:
PMC3333182
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917603.1

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

Description

Variant summary: MANBA c.693G>A (p.Trp231X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.3e-05 in 265406 control chromosomes. This frequency is lower than expected for a pathogenic variant in MANBA causing Beta-Mannosidosis (2.3e-05 vs 0.0011), allowing no conclusion about variant significance. c.693G>A has been reported in the literature in individuals affected with Beta-Mannosidosis. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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