Variant rs2824751 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000284885.8(TMPRSS15):c.1473G>A(p.Ala491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,480 control chromosomes in the GnomAD database, including 46,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A491A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.22 ( 3733 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42773 hom. )

Consequence

TMPRSS15
ENST00000284885.8 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.794

Variant links:

Genes affected

TMPRSS15 (HGNC:9490): (transmembrane serine protease 15) This gene encodes an enzyme that converts the pancreatic proenzyme trypsinogen to trypsin, which activates other proenzymes including chymotrypsinogen and procarboxypeptidases. The precursor protein is cleaved into two chains that form a heterodimer linked by a disulfide bond. This protein is a member of the trypsin family of peptidases. Mutations in this gene cause enterokinase deficiency, a malabsorption disorder characterized by diarrhea and failure to thrive. [provided by RefSeq, Jul 2008]

TMPRSS15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 21-18341504-C-T is Benign according to our data. Variant chr21-18341504-C-T is described in ClinVar as [Benign]. Clinvar id is 2008136.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.794 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS15	NM_002772.3 linkuse as main transcript	c.1473G>A	p.Ala491=	synonymous_variant	13/25	ENST00000284885.8	NP_002763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000284885.8 linkuse as main transcript	c.1473G>A	p.Ala491=	synonymous_variant	13/25	1	NM_002772.3	ENSP00000284885	P1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32696

AN:

151972

Hom.:

3732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.222

AC:

55886

AN:

251402

Hom.:

6638

AF XY:

0.228

AC XY:

30992

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.239

AC:

349559

AN:

1461390

Hom.:

42773

Cov.:

AF XY:

0.241

AC XY:

174902

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.215

AC:

32706

AN:

152090

Hom.:

3733

Cov.:

AF XY:

0.217

AC XY:

16108

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.233

Hom.:

6044

Bravo

AF:

0.206

EpiCase

AF:

0.251

EpiControl

AF:

0.245

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.2

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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