Variant 11-118099062-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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:

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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=0.24004635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS4	NM_019894.4 link	c.121C>G	p.Leu41Val	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 link	c.121C>G	p.Leu41Val	missense_variant	3/13	1	NM_019894.4	ENSP00000416037.3		Q9NRS4-1
TMPRSS4	ENST00000522824.5 link	c.121C>G	p.Leu41Val	missense_variant	3/13	1		ENSP00000430547.1		Q9NRS4-2

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

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.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.121C>G (p.L41V) alteration is located in exon 3 (coding exon 3) of the TMPRSS4 gene. This alteration results from a C to G substitution at nucleotide position 121, causing the leucine (L) at amino acid position 41 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;.;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.64

T;T;.;T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.5

L;.;L;L;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

.;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.12

.;T;T;T;D

Sift4G

Benign

0.28

T;T;T;T;D

Polyphen

0.97

D;D;D;.;.

Vest4

0.24

MutPred

0.31

Loss of catalytic residue at L41 (P = 0.2948);.;Loss of catalytic residue at L41 (P = 0.2948);Loss of catalytic residue at L41 (P = 0.2948);.;

MVP

0.60

MPC

0.13

ClinPred

0.28

GERP RS

3.4

Varity_R

0.081

gMVP

0.38

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

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