Variant 4-68234505-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000332644.6(TMPRSS11B):c.427A>G(p.Met143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,884 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TMPRSS11B
ENST00000332644.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

TMPRSS11B (HGNC:25398): (transmembrane serine protease 11B) Enables serine-type peptidase activity. Predicted to be involved in proteolysis. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMPRSS11B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032175303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMPRSS11B	NM_182502.3 linkuse as main transcript	c.427A>G	p.Met143Val	missense_variant	5/10	ENST00000332644.6	NP_872308.2
TMPRSS11B	XM_011531608.3 linkuse as main transcript	c.427A>G	p.Met143Val	missense_variant	5/11		XP_011529910.1
TMPRSS11B	XM_011531609.1 linkuse as main transcript	c.427A>G	p.Met143Val	missense_variant	5/8		XP_011529911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11B	ENST00000332644.6 linkuse as main transcript	c.427A>G	p.Met143Val	missense_variant	5/10	1	NM_182502.3	ENSP00000330475	P1
TMPRSS11B	ENST00000502365.1 linkuse as main transcript	n.560A>G		non_coding_transcript_exon_variant	5/6	1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152208

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000167

AC:

AN:

251262

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135792

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:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1461676

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727138

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000151

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74370

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

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

Oct 20, 2023

The c.427A>G (p.M143V) alteration is located in exon 5 (coding exon 5) of the TMPRSS11B gene. This alteration results from a A to G substitution at nucleotide position 427, causing the methionine (M) at amino acid position 143 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

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.020

DANN

Benign

0.35

DEOGEN2

Benign

0.0091

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.26

M_CAP

Benign

0.041

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.29

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.12

REVEL

Benign

0.14

Sift

Benign

0.44

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.15

MVP

0.12

MPC

0.028

ClinPred

0.98

GERP RS

-5.9

Varity_R

0.033

gMVP

0.32

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

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