11-118099072-C-T

Position:

chr11-118099072-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The ENST00000437212.8(TMPRSS4):c.131C>T(p.Ala44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,613,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/25 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

TMPRSS4
ENST00000437212.8 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.549

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:

TMPRSS4 (HGNC:):

TMPRSS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-118099072-C-T is Benign according to our data. Variant chr11-118099072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1315695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS4	NM_019894.4 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	3/13	ENST00000437212.8	NP_063947.2	Q9NRS4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	3/13	1	NM_019894.4	ENSP00000416037.3		Q9NRS4-1
TMPRSS4	ENST00000522824.5 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	3/13	1		ENSP00000430547.1		Q9NRS4-2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000279

AC:

AN:

251342

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000498

AC:

728

AN:

1461762

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

334

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000567

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000355

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 21, 2019	Has not been previously published as pathogenic or benign to our knowledge; Although in silico splice predictors suggest this variant may impact gene splicing, additional in silico analyses, which include protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 30919572) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Benign

0.018

T;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.64

T;T;.;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.026

T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.2

L;.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.89

.;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.49

.;T;T;T;T

Sift4G

Benign

0.87

T;T;T;T;T

Polyphen

0.017

B;B;B;.;.

Vest4

0.18

MVP

0.38

MPC

0.12

ClinPred

0.0026

GERP RS

-4.5

Varity_R

0.023

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.97

Position offset: -2

DS_DL_spliceai

0.98

Position offset: 26

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