19-2389833-G-C

Position:

chr19-2389833-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395513.1(TMPRSS9):c.48G>C(p.Lys16Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000519 in 1,613,860 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 2 hom. )

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

TMPRSS9 (HGNC:30079): (transmembrane serine protease 9) The protein encoded by this gene is a membrane-bound type II serine polyprotease that is cleaved to release three different proteases. Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. This gene enhances the invasive capability of pancreatic cancer cells and may be involved in cancer progression. [provided by RefSeq, Jul 2016]

TMPRSS9 links:

TMPRSS9 (HGNC:):

TMPRSS9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012656599).

BP6

Variant 19-2389833-G-C is Benign according to our data. Variant chr19-2389833-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2648970.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	2/19	ENST00000696167.1	NP_001382442.1
TMPRSS9	NM_182973.3 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	2/18		NP_892018.1	Q7Z410Q0X0F2
TMPRSS9	XM_011527978.3 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	2/19		XP_011526280.1	A0A3B3IU58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMPRSS9	ENST00000696167.1 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	2/19		NM_001395513.1	ENSP00000512457.1	A0A3B3IU58
TMPRSS9	ENST00000395264.3 linkuse as main transcript	n.63G>C		non_coding_transcript_exon_variant	1/10	1
TMPRSS9	ENST00000648592.1 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	1/18			ENSP00000498031.1	A0A3B3IU58
TMPRSS9	ENST00000649857.1 linkuse as main transcript	c.48G>C	p.Lys16Asn	missense_variant	2/18			ENSP00000497651.1	Q7Z410

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000813

AC:

204

AN:

250788

Hom.:

AF XY:

0.000855

AC XY:

116

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00241

Gnomad NFE exome

AF:

0.000971

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000515

AC:

753

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

392

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.000464

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000558

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000987

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000857

AC:

104

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TMPRSS9: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0028

T;.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

.;T;T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.3

M;.;.;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

.;.;.;N

REVEL

Benign

0.28

Sift

Pathogenic

0.0

.;.;.;D

Sift4G

Pathogenic

0.0

.;.;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.42, 0.40

MutPred

0.22

Loss of ubiquitination at K16 (P = 0.0127);Loss of ubiquitination at K16 (P = 0.0127);Loss of ubiquitination at K16 (P = 0.0127);Loss of ubiquitination at K16 (P = 0.0127);

MVP

0.85

MPC

0.24

ClinPred

0.073

GERP RS

2.2

Varity_R

0.21

gMVP

0.29

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