Genetic Variant TMPRSS5:p.Ala391Ser (chr11-113690266-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030770.4(TMPRSS5):c.1171G>T(p.Ala391Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000892 in 1,559,782 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00094 ( 3 hom. )

Consequence

TMPRSS5
NM_030770.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

TMPRSS5 (HGNC:14908): (transmembrane serine protease 5) This gene encodes a protein that belongs to the serine protease family. Serine proteases are known to be involved in many physiological and pathological processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034849584).

BP6

Variant 11-113690266-C-A is Benign according to our data. Variant chr11-113690266-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317769.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4 link	c.1171G>T	p.Ala391Ser	missense_variant	Exon 11 of 13	ENST00000299882.11	NP_110397.2	Q9H3S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11 link	c.1171G>T	p.Ala391Ser	missense_variant	Exon 11 of 13	1	NM_030770.4	ENSP00000299882.5		Q9H3S3

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

151564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000728

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:

0.000856

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000679

AC:

115

AN:

169452

Hom.:

AF XY:

0.000622

AC XY:

AN XY:

90094

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.0000394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.000944

AC:

1329

AN:

1408102

Hom.:

Cov.:

AF XY:

0.000882

AC XY:

613

AN XY:

695288

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00222

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000581

GnomAD4 genome

AF:

0.000409

AC:

AN:

151680

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000856

Gnomad4 NFE

AF:

0.000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.000591

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;D;D;D;D;.;D;D

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

.;T;T;D;D;T;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.035

T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

3.3

M;M;.;.;.;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.8

.;D;D;D;D;D;D;D

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

.;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

.;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;.;D;.

Vest4

0.72, 0.71, 0.77, 0.67, 0.72, 0.80, 0.75

MVP

0.91

MPC

0.40

ClinPred

0.25

GERP RS

4.2

Varity_R

0.91

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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