Genetic Variant TMPRSS9:p.Thr82Arg (chr19-2396641-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395513.1(TMPRSS9):c.245C>G(p.Thr82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T82M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.438

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TMPRSS9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09371436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395513.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS9	NM_001395513.1	MANE Select	c.245C>G	p.Thr82Arg	missense	Exon 3 of 19	NP_001382442.1	A0A3B3IU58
TMPRSS9	NM_182973.3		c.245C>G	p.Thr82Arg	missense	Exon 3 of 18	NP_892018.1	Q7Z410
TMPRSS9	NM_001385642.1		c.-452C>G		5_prime_UTR	Exon 2 of 18	NP_001372571.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS9	ENST00000696167.1	MANE Select	c.245C>G	p.Thr82Arg	missense	Exon 3 of 19	ENSP00000512457.1	A0A3B3IU58
TMPRSS9	ENST00000395264.3	TSL:1	n.260C>G		non_coding_transcript_exon	Exon 2 of 10
TMPRSS9	ENST00000648592.1		c.245C>G	p.Thr82Arg	missense	Exon 2 of 18	ENSP00000498031.1	A0A3B3IU58

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000253

AC:

AN:

237182

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455408

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.000161

AC:

AN:

43424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25888

East Asian (EAS)

AF:

0.00

AC:

AN:

39470

South Asian (SAS)

AF:

0.00

AC:

AN:

85048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109572

Other (OTH)

AF:

0.00

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.29

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.7

PhyloP100

-0.44

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Benign

0.20

Sift

Benign

0.17

Sift4G

Benign

0.082

Polyphen

0.039

Vest4

0.26

MutPred

0.29

Gain of MoRF binding (P = 0.0307)

MVP

0.52

MPC

0.16

ClinPred

0.019

GERP RS

-3.0

Varity_R

0.078

gMVP

0.48

Mutation Taster

=94/6

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over