Variant 21-18359856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The ENST00000284885.8(TMPRSS15):c.781C>T(p.Gln261Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000757 in 1,320,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

TMPRSS15
ENST00000284885.8 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 5.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 21-18359856-G-A is Pathogenic according to our data. Variant chr21-18359856-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 4166.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS15	NM_002772.3 linkuse as main transcript	c.781C>T	p.Gln261Ter	stop_gained	8/25	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.781C>T	p.Gln261Ter	stop_gained	8/25	1	NM_002772.3	ENSP00000284885	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248082

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.57e-7

AC:

AN:

1320996

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000526

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Enterokinase deficiency

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2002	- -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	Oct 01, 2021	PVS1, PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.82

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.89

MutationTaster

Benign

1.0

Vest4

0.35

GERP RS

4.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.51

Position offset: 7

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