dbSNP rs149423953: TMPRSS4:p.Arg20Ser (chr11-118098999-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_019894.4(TMPRSS4):c.58C>A(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TMPRSS4
NM_019894.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

Variant links:

Genes affected

TMPRSS4 (HGNC:11878): (transmembrane serine protease 4) This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

TMPRSS4 links:

LOC105369517 (HGNC:):

LOC105369517 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=0.0793328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS4	NM_019894.4 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 3 of 13	ENST00000437212.8	NP_063947.2	Q9NRS4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 3 of 13	1	NM_019894.4	ENSP00000416037.3		Q9NRS4-1
TMPRSS4	ENST00000522824.5 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 3 of 13	1		ENSP00000430547.1		Q9NRS4-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250714

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135486

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:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461238

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

726900

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:

0.000603

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000502

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000576

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.4

DANN

Benign

0.79

DEOGEN2

Benign

0.016

T;.;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.66

T;T;.;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.079

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;.;L;L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.33

.;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.21

.;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.028

B;B;B;.;.

Vest4

0.32

MutPred

0.34

Gain of phosphorylation at R20 (P = 0.0346);.;Gain of phosphorylation at R20 (P = 0.0346);Gain of phosphorylation at R20 (P = 0.0346);.;

MVP

0.67

MPC

0.15

ClinPred

0.029

GERP RS

0.93

Varity_R

0.077

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over