Variant 19-2389868-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395513.1(TMPRSS9):c.83C>G(p.Ala28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.68

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10103053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1 linkuse as main transcript	c.83C>G	p.Ala28Gly	missense_variant	2/19	ENST00000696167.1	NP_001382442.1
TMPRSS9	NM_182973.3 linkuse as main transcript	c.83C>G	p.Ala28Gly	missense_variant	2/18		NP_892018.1	Q7Z410Q0X0F2
TMPRSS9	XM_011527978.3 linkuse as main transcript	c.83C>G	p.Ala28Gly	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.83C>G	p.Ala28Gly	missense_variant	2/19		NM_001395513.1	ENSP00000512457.1	A0A3B3IU58
TMPRSS9	ENST00000395264.3 linkuse as main transcript	n.98C>G		non_coding_transcript_exon_variant	1/10	1
TMPRSS9	ENST00000648592.1 linkuse as main transcript	c.83C>G	p.Ala28Gly	missense_variant	1/18			ENSP00000498031.1	A0A3B3IU58
TMPRSS9	ENST00000649857.1 linkuse as main transcript	c.83C>G	p.Ala28Gly	missense_variant	2/18			ENSP00000497651.1	Q7Z410

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152176

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251052

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135808

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:

0.000132

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000149

AC:

218

AN:

1461712

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727136

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:

0.0000188

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

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:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.83C>G (p.A28G) alteration is located in exon 1 (coding exon 1) of the TMPRSS9 gene. This alteration results from a C to G substitution at nucleotide position 83, causing the alanine (A) at amino acid position 28 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.0030

DANN

Benign

0.77

DEOGEN2

Benign

0.0057

T;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.31

.;T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.4

L;.;.;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

.;.;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.36

.;.;.;T

Sift4G

Benign

0.068

.;.;T;T

Polyphen

0.39

B;.;.;B

Vest4

0.15, 0.14

MVP

0.39

MPC

0.077

ClinPred

0.096

GERP RS

-8.8

Varity_R

0.032

gMVP

0.14

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