NM_001256317.3(TMPRSS3):c.917C>T (p.Ala306Val) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 13, 2022
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:: RCV003708734.2

Allele description [Variation Report for NM_001256317.3(TMPRSS3):c.917C>T (p.Ala306Val)]

NM_001256317.3(TMPRSS3):c.917C>T (p.Ala306Val)

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.917C>T (p.Ala306Val)

HGVS:

NC_000021.9:g.42382100G>A
NG_011629.2:g.18992C>T
NM_001256317.3:c.917C>TMANE SELECT
NM_024022.4:c.917C>T
NM_032404.3:c.536C>T
NM_032405.2:c.917C>T
NP_001243246.1:p.Ala306Val
NP_076927.1:p.Ala306Val
NP_115780.1:p.Ala179Val
NP_115781.1:p.Ala306Val
NC_000021.8:g.43802209G>A

Protein change:

A179V

Molecular consequence:

NM_001256317.3:c.917C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024022.4:c.917C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032404.3:c.536C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032405.2:c.917C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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LOC4329057 [Oryza sativa Japonica Group]
LOC4329057 [Oryza sativa Japonica Group]
Gene ID:4329057

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004485988	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 13, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17551081, 23208854, 24526180, 28246597, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004485988

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 13, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Autosomal recessive postlingual hearing loss (DFNB8): compound heterozygosity for two novel TMPRSS3 mutations in German siblings.

Elbracht M, Senderek J, Eggermann T, Thürmer C, Park J, Westhofen M, Zerres K.

J Med Genet. 2007 Jun;44(6):e81.

PubMed [citation]

PMID:: 17551081
PMCID:: PMC2752172

A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing.

Schrauwen I, Sommen M, Corneveaux JJ, Reiman RA, Hackett NJ, Claes C, Claes K, Bitner-Glindzicz M, Coucke P, Van Camp G, Huentelman MJ.

Am J Med Genet A. 2013 Jan;161A(1):145-52. doi: 10.1002/ajmg.a.35737. Epub 2012 Dec 3.

PubMed [citation]

PMID:: 23208854

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004485988.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has not been reported in the literature in individuals affected with TMPRSS3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 306 of the TMPRSS3 protein (p.Ala306Val). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TMPRSS3 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala306 amino acid residue in TMPRSS3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17551081, 23208854, 24526180, 28246597). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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