rs2824721

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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

Publications

36 publications found

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 Gene-Disease associations (from GenCC):

congenital enteropathy due to enteropeptidase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

TMPRSS15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1995943.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TMPRSS15	NM_002772.3	MANE Select	c.2194C>T	p.Pro732Ser	missense	Exon 19 of 25	NP_002763.3
TMPRSS15	NM_001428056.1		c.2329C>T	p.Pro777Ser	missense	Exon 23 of 29	NP_001414985.1
TMPRSS15	NM_001428057.1		c.2194C>T	p.Pro732Ser	missense	Exon 21 of 27	NP_001414986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS15	ENST00000284885.8	TSL:1 MANE Select	c.2194C>T	p.Pro732Ser	missense	Exon 19 of 25	ENSP00000284885.3

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

GnomAD2 exomes

AF:

0.751

AC:

188709

AN:

251242

AF XY:

0.753

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 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

African (AFR)

AF:

0.702

AC:

23461

AN:

33424

American (AMR)

AF:

0.698

AC:

31222

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.735

AC:

19187

AN:

26106

East Asian (EAS)

AF:

0.674

AC:

26704

AN:

39610

South Asian (SAS)

AF:

0.717

AC:

61778

AN:

86218

European-Finnish (FIN)

AF:

0.808

AC:

43139

AN:

53384

Middle Eastern (MID)

AF:

0.723

AC:

4165

AN:

5760

European-Non Finnish (NFE)

AF:

0.786

AC:

873180

AN:

1110684

Other (OTH)

AF:

0.768

AC:

46337

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

12417

24835

37252

49670

62087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20588

41176

61764

82352

102940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.750

AC:

114035

AN:

152036

Hom.:

42930

Cov.:

AF XY:

0.750

AC XY:

55736

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.705

AC:

29224

AN:

41450

American (AMR)

AF:

0.733

AC:

11195

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2509

AN:

3472

East Asian (EAS)

AF:

0.662

AC:

3419

AN:

5164

South Asian (SAS)

AF:

0.718

AC:

3449

AN:

4804

European-Finnish (FIN)

AF:

0.808

AC:

8540

AN:

10568

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53372

AN:

67988

Other (OTH)

AF:

0.746

AC:

1576

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1478

2955

4433

5910

7388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.768

Hom.:

146237

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

(source)

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

PhyloP100

2.3

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

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over