NM_001256317.3(TMPRSS3):c.280G>A (p.Gly94Arg) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 4, 2019
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:: RCV000506390.14

Allele description [Variation Report for NM_001256317.3(TMPRSS3):c.280G>A (p.Gly94Arg)]

NM_001256317.3(TMPRSS3):c.280G>A (p.Gly94Arg)

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.280G>A (p.Gly94Arg)

HGVS:

NC_000021.9:g.42388971C>T
NG_011629.2:g.12121G>A
NM_001256317.3:c.280G>AMANE SELECT
NM_024022.4:c.280G>A
NM_032404.3:c.-102G>A
NM_032405.2:c.280G>A
NP_001243246.1:p.Gly94Arg
NP_076927.1:p.Gly94Arg
NP_115781.1:p.Gly94Arg
NC_000021.8:g.43809080C>T
NM_024022.2:c.280G>A
NM_024022.3:c.280G>A

Protein change:

G94R

Links:

dbSNP: rs143762350

NCBI 1000 Genomes Browser:

rs143762350

Molecular consequence:

NM_032404.3:c.-102G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001256317.3:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024022.4:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032405.2:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000605390	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Apr 10, 2017)	germline	clinical testing	Citation Link,
SCV000710863	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jan 4, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25770132, 23967202, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000605390

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Apr 10, 2017)

germline

clinical testing

Citation Link,

SCV000710863

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jan 4, 2019)

germline

clinical testing

PubMed (3)
[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
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

The patients associated with TMPRSS3 mutations are good candidates for electric acoustic stimulation.

Miyagawa M, Nishio SY, Sakurai Y, Hattori M, Tsukada K, Moteki H, Kojima H, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:193S-204S. doi: 10.1177/0003489415575056. Epub 2015 Mar 13.

PubMed [citation]

PMID:: 25770132

Targeted exon sequencing successfully discovers rare causative genes and clarifies the molecular epidemiology of Japanese deafness patients.

Miyagawa M, Naito T, Nishio SY, Kamatani N, Usami S.

PLoS One. 2013;8(8):e71381. doi: 10.1371/journal.pone.0071381.

PubMed [citation]

PMID:: 23967202
PMCID:: PMC3742761

See all PubMed Citations (3)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000605390.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000710863.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Gly94Arg variant in TMPRSS3 has been reported in at least 2 individuals wi th hearing loss (Miyagawa 2013, LMM data). It has also been identified in 0.03% (42/129164) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID: 440339). Computational predicti on tools and conservation analysis suggest that the p.Gly94Arg variant may impac t the protein, though this information is not predictive enough to determine pat hogenicity. In summary, the clinical significance of the p.Gly94Arg variant is u ncertain. ACMG/AMP criteria applied: PM2_Supporting, PP3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

Last Updated: Dec 24, 2023

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