Variant chr21-42372183-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001256317.3(TMPRSS3):c.*578del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.35 ( 10727 hom., cov: 0)

Exomes 𝑓: 0.40 ( 25413 hom. )

Consequence

TMPRSS3
NM_001256317.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

TMPRSS3 (HGNC:11877): (transmembrane serine protease 3) This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a serine protease domain, a transmembrane domain, an LDL receptor-like domain, and a scavenger receptor cysteine-rich domain. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified by its association with both congenital and childhood onset autosomal recessive deafness. This gene is expressed in fetal cochlea and many other tissues, and is thought to be involved in the development and maintenance of the inner ear or the contents of the perilymph and endolymph. This gene was also identified as a tumor-associated gene that is overexpressed in ovarian tumors. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

TMPRSS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 21-42372183-AC-A is Benign according to our data. Variant chr21-42372183-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 340042.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TMPRSS3	NM_001256317.3 linkuse as main transcript	c.*578del	3_prime_UTR_variant	13/13	ENST00000644384.2	NP_001243246.1
TMPRSS3	NM_024022.4 linkuse as main transcript	c.*578del	3_prime_UTR_variant	13/13		NP_076927.1
TMPRSS3	NM_032404.3 linkuse as main transcript	c.*578del	3_prime_UTR_variant	10/10		NP_115780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS3	ENST00000644384.2 linkuse as main transcript	c.*578del		3_prime_UTR_variant	13/13		NM_001256317.3	ENSP00000494414	A1	P57727-5

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52532

AN:

151904

Hom.:

10722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.0245

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.374

AC:

48875

AN:

130692

Hom.:

10410

AF XY:

0.370

AC XY:

26345

AN XY:

71284

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.0321

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.503

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.398

AC:

118235

AN:

297062

Hom.:

25413

Cov.:

AF XY:

0.386

AC XY:

65165

AN XY:

168628

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.495

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.346

AC:

52551

AN:

152022

Hom.:

10727

Cov.:

AF XY:

0.344

AC XY:

25542

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.0247

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.507

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.407

Hom.:

2423

Bravo

AF:

0.334

Asia WGS

AF:

0.145

AC:

507

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over