Genetic Variant TMPRSS4:p.Leu41Val (chr11-118099062-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_019894.4(TMPRSS4):c.121C>G(p.Leu41Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMPRSS4
NM_019894.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.791

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive cerebral atrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMPRSS4 links:

LOC105369517 (HGNC:):

LOC105369517 links:

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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=0.24004635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS4	NM_019894.4	MANE Select	c.121C>G	p.Leu41Val	missense	Exon 3 of 13	NP_063947.2	Q9NRS4-1
TMPRSS4	NM_001173551.2		c.115C>G	p.Leu39Val	missense	Exon 3 of 13	NP_001167022.2	Q9NRS4-3
TMPRSS4	NM_001083947.2		c.121C>G	p.Leu41Val	missense	Exon 3 of 13	NP_001077416.2	Q9NRS4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS4	ENST00000437212.8	TSL:1 MANE Select	c.121C>G	p.Leu41Val	missense	Exon 3 of 13	ENSP00000416037.3	Q9NRS4-1
TMPRSS4	ENST00000522824.5	TSL:1	c.121C>G	p.Leu41Val	missense	Exon 3 of 13	ENSP00000430547.1	Q9NRS4-2
TMPRSS4	ENST00000714375.1		n.121C>G		non_coding_transcript_exon	Exon 3 of 12	ENSP00000519642.1	A0AAQ5BHV3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60392

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.031

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.64

M_CAP

Benign

0.047

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.5

PhyloP100

0.79

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.33

Sift

Benign

0.12

Sift4G

Benign

0.28

Polyphen

0.97

Vest4

0.24

MutPred

0.31

Loss of catalytic residue at L41 (P = 0.2948)

MVP

0.60

MPC

0.13

ClinPred

0.28

GERP RS

3.4

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.081

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over