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NM_002700.3(POU4F3):c.745C>A (p.Gln249Lys) AND Autosomal dominant nonsyndromic hearing loss 15

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 19, 2020
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:
RCV002471224.1

Allele description [Variation Report for NM_002700.3(POU4F3):c.745C>A (p.Gln249Lys)]

NM_002700.3(POU4F3):c.745C>A (p.Gln249Lys)

Genes:
POU4F3:POU class 4 homeobox 3 [Gene - OMIM - HGNC]
LOC127814297:RBM27-POU4F3 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
5q32
Genomic location:
Preferred name:
NM_002700.3(POU4F3):c.745C>A (p.Gln249Lys)
HGVS:
  • NC_000005.10:g.146340172C>A
  • NG_011885.1:g.6149C>A
  • NM_002700.3:c.745C>AMANE SELECT
  • NP_002691.1:p.Gln249Lys
  • LRG_1355t1:c.745C>A
  • LRG_1355:g.6149C>A
  • LRG_1355p1:p.Gln249Lys
  • NC_000005.9:g.145719735C>A
  • NM_002700.2:c.745C>A
Protein change:
Q249K
Links:
dbSNP: rs1465371108
NCBI 1000 Genomes Browser:
rs1465371108
Molecular consequence:
  • NM_002700.3:c.745C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal dominant nonsyndromic hearing loss 15
Synonyms:
Deafness, autosomal dominant 15
Identifiers:
MONDO: MONDO:0011226; MedGen: C1865366; Orphanet: 90635; OMIM: 602459

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767847Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 19, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767847.1

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

Description

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant deafness (OMIM). (N) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to lycine. This variant is in exon 2 of 2 of the POU4F3 gene. (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD v2 <0.001 for a dominant condition (2 Heterozygotes, 0 Homozygotes). (P) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif. This variant is in the POU-specific domain (NCBI conserved domain). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant in the literature. (N) 1007 - No published functional evidence has been identified for this variant in the literature. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

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

Last Updated: Mar 5, 2024