Genetic Variant TMPRSS9:p.Arg81Ser (chr19-2396637-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001395513.1(TMPRSS9):c.241C>A(p.Arg81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0390

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.275117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1 link	c.241C>A	p.Arg81Ser	missense_variant	Exon 3 of 19	ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1 link	c.241C>A	p.Arg81Ser	missense_variant	Exon 3 of 19		NM_001395513.1	ENSP00000512457.1		A0A3B3IU58

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1454216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722762

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.241C>A (p.R81S) alteration is located in exon 2 (coding exon 2) of the TMPRSS9 gene. This alteration results from a C to A substitution at nucleotide position 241, causing the arginine (R) at amino acid position 81 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0091

T;.;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.72

.;T;T;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Uncertain

-0.030

MutationAssessor

Uncertain

2.2

M;.;.;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.8

.;.;.;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.018

.;.;.;D

Sift4G

Uncertain

0.017

.;.;D;D

Polyphen

0.97

D;.;.;D

Vest4

0.60, 0.51

MutPred

0.37

Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);

MVP

0.77

MPC

0.24

ClinPred

0.94

GERP RS

1.6

Varity_R

0.14

gMVP

0.41

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over