NM_015404.4(WHRN):c.1126G>T (p.Ala376Ser) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jan 9, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000607742.1

Allele description [Variation Report for NM_015404.4(WHRN):c.1126G>T (p.Ala376Ser)]

NM_015404.4(WHRN):c.1126G>T (p.Ala376Ser)

Gene:
WHRN:whirlin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q32
Genomic location:
Preferred name:
NM_015404.4(WHRN):c.1126G>T (p.Ala376Ser)
HGVS:
  • NC_000009.12:g.114426251C>A
  • NG_016700.1:g.84206G>T
  • NM_001083885.2:c.-24G>T
  • NM_001173425.2:c.1126G>T
  • NM_015404.4:c.1126G>TMANE SELECT
  • NP_001166896.1:p.Ala376Ser
  • NP_056219.3:p.Ala376Ser
  • LRG_1094t1:c.1126G>T
  • LRG_1094:g.84206G>T
  • LRG_1094p1:p.Ala376Ser
  • NC_000009.11:g.117188531C>A
  • NM_015404.3:c.1126G>T
Protein change:
A376S
Links:
dbSNP: rs545251395
NCBI 1000 Genomes Browser:
rs545251395
Molecular consequence:
  • NM_001083885.2:c.-24G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001173425.2:c.1126G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015404.4:c.1126G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000713801Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jan 9, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000713801.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Ala376Ser var iant in WHRN has not been previously reported in individuals with hearing loss, but has been identified in 0.09% (28/30778) of South Asian chromosomes including 1 homozygote by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs545251395). Computational prediction tools and conservation analysis suggest that the p.Ala376Ser variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary , while the clinical significance of the p.Ala376Ser variant is uncertain, avail able data suggest that this variant is more likely to be benign. ACMG/AMP criter ia applied: BP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jul 7, 2021

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