NM_181697.3(PRDX1):c.515-2A>T AND METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE, DIGENIC

Clinical significance:Pathogenic (Last evaluated: Sep 27, 2018)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000585793.3

Allele description [Variation Report for NM_181697.3(PRDX1):c.515-2A>T]

NM_181697.3(PRDX1):c.515-2A>T

Genes:
MMACHC:metabolism of cobalamin associated C [Gene - OMIM - HGNC]
PRDX1:peroxiredoxin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_181697.3(PRDX1):c.515-2A>T
HGVS:
  • NC_000001.11:g.45511416T>A
  • NG_013378.1:g.16233T>A
  • NM_001202431.2:c.515-2A>T
  • NM_001330540.2:c.*2201T>A
  • NM_002574.4:c.515-2A>T
  • NM_015506.3:c.*2201T>AMANE SELECT
  • NM_181696.3:c.515-2A>T
  • NM_181697.3:c.515-2A>TMANE SELECT
  • NC_000001.10:g.45977088T>A
  • NM_181697.2:c.515-2A>T
Nucleotide change:
IVS5AS, -2, A-T
Links:
OMIM: 176763.0002; dbSNP: rs1379672870
NCBI 1000 Genomes Browser:
rs1379672870
Molecular consequence:
  • NM_001330540.2:c.*2201T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_015506.3:c.*2201T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001202431.2:c.515-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_002574.4:c.515-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181696.3:c.515-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181697.3:c.515-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE, DIGENIC
Identifiers:
MedGen: C4693974

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000693722OMIMno assertion criteria providedPathogenic
(Sep 27, 2018)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients.

Guéant JL, Chéry C, Oussalah A, Nadaf J, Coelho D, Josse T, Flayac J, Robert A, Koscinski I, Gastin I, Filhine-Tresarrieu P, Pupavac M, Brebner A, Watkins D, Pastinen T, Montpetit A, Hariri F, Tregouët D, Raby BA, Chung WK, Morange PE, Froese DS, et al.

Nat Commun. 2018 Feb 2;9(1):554. doi: 10.1038/s41467-018-03054-w.

PubMed [citation]
PMID:
29396438
PMCID:
PMC5797229

Details of each submission

From OMIM, SCV000693722.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a female (WG-3838) of Japanese and Korean ancestry with cbl-type methylmalonic aciduria and homocystinuria (MAHCC; 277400), who died at 2 months of age, Gueant et al. (2018) identified compound heterozygous mutations in the MMACHC gene: a splice site mutation (c.81G-A; 609831.0012) inherited from the mother, and a secondary epimutation causing promoter hypermethylation and MMACHC silencing inherited from the father. The secondary epimutation was triggered by a heterozygous splice site mutation (c.515-2A-T) in the adjacent, reverse-oriented PRDX1 gene. The mutation caused skipping of exon 6 and the polyA transcription termination signal of PRDX1, producing an aberrant extension of antisense transcription through the MMACHC AND CCDC163P genes.

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

Last Updated: Oct 24, 2021

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