Variant chr4-67919023-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001114387.2(TMPRSS11A):c.902A>C(p.Gln301Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TMPRSS11A
NM_001114387.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

TMPRSS11A (HGNC:27954): (transmembrane serine protease 11A) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMPRSS11A links:

UBA6-DT (HGNC:):

UBA6-DT 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=0.017982453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11A	NM_001114387.2 linkuse as main transcript	c.902A>C	p.Gln301Pro	missense_variant	8/10	ENST00000508048.6	NP_001107859.1	Q6ZMR5A8KA85
TMPRSS11A	NM_182606.4 linkuse as main transcript	c.911A>C	p.Gln304Pro	missense_variant	8/10		NP_872412.3	Q6ZMR5A0A0A0MR82A8KA85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11A	ENST00000508048.6 linkuse as main transcript	c.902A>C	p.Gln301Pro	missense_variant	8/10	1	NM_001114387.2	ENSP00000426911.2		Q6ZMR5

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251474

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000101

AC:

147

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000872

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:

0.0000809

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000269

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

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

Jun 03, 2022

The c.911A>C (p.Q304P) alteration is located in exon 8 (coding exon 8) of the TMPRSS11A gene. This alteration results from a A to C substitution at nucleotide position 911, causing the glutamine (Q) at amino acid position 304 to be replaced by a proline (P). 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

0.067

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.13

DANN

Benign

0.75

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.78

PrimateAI

Benign

0.27

PROVEAN

Benign

1.2

.;N;N

REVEL

Benign

0.22

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.26

T;T;T

Vest4

0.15

MVP

0.20

MPC

0.12

ClinPred

0.017

GERP RS

-4.6

gMVP

0.70

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

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