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NM_172166.4(MSH5):c.1459G>T (p.Asp487Tyr) AND Premature ovarian failure 13

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 28, 2022
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000477966.6

Allele description [Variation Report for NM_172166.4(MSH5):c.1459G>T (p.Asp487Tyr)]

NM_172166.4(MSH5):c.1459G>T (p.Asp487Tyr)

Genes:
MSH5-SAPCD1:MSH5-SAPCD1 readthrough (NMD candidate) [Gene - HGNC]
MSH5:mutS homolog 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.33
Genomic location:
Preferred name:
NM_172166.4(MSH5):c.1459G>T (p.Asp487Tyr)
HGVS:
  • NC_000006.12:g.31759476G>T
  • NG_011611.1:g.24480G>T
  • NM_002441.5:c.1459G>T
  • NM_025259.6:c.1510G>T
  • NM_172165.4:c.1459G>T
  • NM_172166.4:c.1459G>TMANE SELECT
  • NP_002432.1:p.Asp487Tyr
  • NP_079535.4:p.Asp504Tyr
  • NP_751897.1:p.Asp487Tyr
  • NP_751897.1:p.Asp487Tyr
  • NP_751898.1:p.Asp487Tyr
  • NC_000006.11:g.31727253G>T
  • NM_172165.3:c.1459G>T
  • NR_037846.1:n.1638G>T
Protein change:
D487Y; ASP487TYR
Links:
OMIM: 603382.0001; dbSNP: rs1060505055
NCBI 1000 Genomes Browser:
rs1060505055
Molecular consequence:
  • NM_002441.5:c.1459G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_025259.6:c.1510G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172165.4:c.1459G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172166.4:c.1459G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_037846.1:n.1638G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Premature ovarian failure 13 (POF13)
Identifiers:
MONDO: MONDO:0044317; MedGen: C4479510; OMIM: 617442

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000564402OMIM
no assertion criteria provided
Pathogenic
(Jun 28, 2022) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Mutations in MSH5 in primary ovarian insufficiency.

Guo T, Zhao S, Zhao S, Chen M, Li G, Jiao X, Wang Z, Zhao Y, Qin Y, Gao F, Chen ZJ.

Hum Mol Genet. 2017 Apr 15;26(8):1452-1457. doi: 10.1093/hmg/ddx044.

PubMed [citation]
PMID:
28175301
PMCID:
PMC5393145

Details of each submission

From OMIM, SCV000564402.6

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

Description

In 2 Han Chinese sisters with premature ovarian failure (POF13; 617442), Guo et al. (2017) identified homozygosity for a c.1459G-T transversion (c.1459G-T, ENST00000375755) in the MSH5 gene, resulting in an asp487-to-tyr (D487Y) substitution at a highly conserved residue within the DNA-binding domain. The mutation segregated fully with disease in the family and was not found in 400 fertile women. Mutant female mice homozygous for the homologous mutation in Msh5 were infertile and had no developing follicles or germ cells in their ovaries. Functional analysis in U2OS cells overexpressing the D487Y mutant showed more unrepaired double-stranded DNA breaks than wildtype control cells. In addition, HeLa cells overexpressing mutant MSH5 showed a lower clonogenic survival rate compared to wildtype.

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

Last Updated: Jul 8, 2022