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NM_001256317.3(TMPRSS3):c.727G>A (p.Gly243Arg) AND Autosomal recessive nonsyndromic hearing loss 8

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 16, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000487440.5

Allele description [Variation Report for NM_001256317.3(TMPRSS3):c.727G>A (p.Gly243Arg)]

NM_001256317.3(TMPRSS3):c.727G>A (p.Gly243Arg)

Gene:
TMPRSS3:transmembrane serine protease 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_001256317.3(TMPRSS3):c.727G>A (p.Gly243Arg)
HGVS:
  • NC_000021.9:g.42383088C>T
  • NG_011629.2:g.18004G>A
  • NM_001256317.1:c.727G>A
  • NM_001256317.3:c.727G>AMANE SELECT
  • NM_024022.4:c.727G>A
  • NM_032404.3:c.346G>A
  • NM_032405.2:c.727G>A
  • NP_001243246.1:p.Gly243Arg
  • NP_076927.1:p.Gly243Arg
  • NP_115780.1:p.Gly116Arg
  • NP_115781.1:p.Gly243Arg
  • NC_000021.8:g.43803197C>T
  • NM_024022.2:c.727G>A
  • NM_024022.4:c.727G>A
Protein change:
G116R
Links:
dbSNP: rs372526764
NCBI 1000 Genomes Browser:
rs372526764
Molecular consequence:
  • NM_001256317.3:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024022.4:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032404.3:c.346G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032405.2:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 8
Synonyms:
NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 8; Deafness, autosomal recessive 8; Deafness, autosomal recessive 10
Identifiers:
MONDO: MONDO:0010987; MedGen: C1832827; Orphanet: 90636; OMIM: 601072

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000574531GenePathDx, GenePath diagnostics
criteria provided, single submitter

(GenePathDx_Criteria_classificationV2)		Likely pathogenic
(May 1, 2016) 		germlineclinical testing

GenePathDx_Criteria_classificationV2.doc,

Citation Link,

SCV005395879Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Sep 16, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes11not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Non-syndromic hearing impairment in India: high allelic heterogeneity among mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE.

Ganapathy A, Pandey N, Srisailapathy CR, Jalvi R, Malhotra V, Venkatappa M, Chatterjee A, Sharma M, Santhanam R, Chadha S, Ramesh A, Agarwal AK, Rangasayee RR, Anand A.

PLoS One. 2014;9(1):e84773. doi: 10.1371/journal.pone.0084773.

PubMed [citation]
PMID:
24416283
PMCID:
PMC3885616

Sequence variants in genes causing nonsyndromic hearing loss in a Pakistani cohort.

Khan A, Han S, Wang R, Ansar M, Ahmad W, Zhang X.

Mol Genet Genomic Med. 2019 Sep;7(9):e917. doi: 10.1002/mgg3.917. Epub 2019 Aug 6.

PubMed [citation]
PMID:
31389194
PMCID:
PMC6732339

Details of each submission

From GenePathDx, GenePath diagnostics, SCV000574531.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

12 years old child with deafness and a history of parental consanguinity. Next generation DNA sequencing of peripheral blood sample has revealed presence of a homozygous variant c.727 G>A in exon 8 of TMPRSS3 gene. This variant was predicted to be likely pathogenic based on available evidences in the databases and in silico mutation prediction methods.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005395879.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: TMPRSS3 c.727G>A (p.Gly243Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251270 control chromosomes (gnomAD). c.727G>A has been reported in the literature in multiple individuals affected with Deafness, Autosomal Recessive 8 (e.g. Ganapathy_2014, Khan_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 24416283, 31389194). ClinVar contains an entry for this variant (Variation ID: 178549). 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 18, 2024