chr19-2389816-G-A

Position:

chr19-2389816-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001395513.1(TMPRSS9):c.31G>A(p.Val11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0680

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13178375).

BP6

Variant 19-2389816-G-A is Benign according to our data. Variant chr19-2389816-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2309087.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	2/19	ENST00000696167.1	NP_001382442.1
TMPRSS9	NM_182973.3 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	2/18		NP_892018.1	Q7Z410Q0X0F2
TMPRSS9	XM_011527978.3 linkuse as main transcript	c.31G>A	p.Val11Met	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.31G>A	p.Val11Met	missense_variant	2/19		NM_001395513.1	ENSP00000512457.1	A0A3B3IU58
TMPRSS9	ENST00000395264.3 linkuse as main transcript	n.46G>A		non_coding_transcript_exon_variant	1/10	1
TMPRSS9	ENST00000648592.1 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	1/18			ENSP00000498031.1	A0A3B3IU58
TMPRSS9	ENST00000649857.1 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	2/18			ENSP00000497651.1	Q7Z410

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250424

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461534

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;.;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.47

.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.3

M;.;.;M

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.59

.;.;.;N

REVEL

Benign

0.20

Sift

Uncertain

0.0040

.;.;.;D

Sift4G

Uncertain

0.0070

.;.;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.17, 0.25

MutPred

0.28

Gain of catalytic residue at V11 (P = 0.0399);Gain of catalytic residue at V11 (P = 0.0399);Gain of catalytic residue at V11 (P = 0.0399);Gain of catalytic residue at V11 (P = 0.0399);

MVP

0.54

MPC

0.087

ClinPred

0.24

GERP RS

-0.27

Varity_R

0.048

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