Variant 21-18297801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002772.3(TMPRSS15):c.2194C>T(p.Pro732Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,612,248 control chromosomes in the GnomAD database, including 480,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 42930 hom., cov: 31)

Exomes 𝑓: 0.77 ( 437723 hom. )

Consequence

TMPRSS15
NM_002772.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.796112E-7).

BP6

Variant 21-18297801-G-A is Benign according to our data. Variant chr21-18297801-G-A is described in ClinVar as [Benign]. Clinvar id is 1995943.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-18297801-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 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.2194C>T	p.Pro732Ser	missense_variant	19/25	ENST00000284885.8	NP_002763.3	P98073

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000284885.8 linkuse as main transcript	c.2194C>T	p.Pro732Ser	missense_variant	19/25	1	NM_002772.3	ENSP00000284885.3		P98073

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

113950

AN:

151918

Hom.:

42889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.751

AC:

188709

AN:

251242

Hom.:

71371

AF XY:

0.753

AC XY:

102289

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.706

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.790

Gnomad OTH exome

AF:

0.757

GnomAD4 exome

AF:

0.773

AC:

1129173

AN:

1460212

Hom.:

437723

Cov.:

AF XY:

0.772

AC XY:

560693

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.702

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.717

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.786

Gnomad4 OTH exome

AF:

0.768

GnomAD4 genome

AF:

0.750

AC:

114035

AN:

152036

Hom.:

42930

Cov.:

AF XY:

0.750

AC XY:

55736

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.705

Gnomad4 AMR

AF:

0.733

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.785

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.771

Hom.:

110591

Bravo

AF:

0.739

TwinsUK

AF:

0.788

AC:

2922

ALSPAC

AF:

0.778

AC:

2997

ESP6500AA

AF:

0.705

AC:

3108

ESP6500EA

AF:

0.783

AC:

6734

ExAC

AF:

0.754

AC:

91567

Asia WGS

AF:

0.700

AC:

2434

AN:

3478

EpiCase

AF:

0.781

EpiControl

AF:

0.775

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

DANN

Benign

0.11

DEOGEN2

Benign

0.012

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.27

MetaRNN

Benign

9.8e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.6

PrimateAI

Benign

0.40

PROVEAN

Benign

1.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MPC

0.028

ClinPred

0.0043

GERP RS

5.7

Varity_R

0.022

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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