Variant 2-217809974-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001387777.1(TNS1):c.5122G>A(p.Val1708Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,613,192 control chromosomes in the GnomAD database, including 293,610 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.64 ( 32124 hom., cov: 32)

Exomes 𝑓: 0.60 ( 261486 hom. )

Consequence

TNS1
NM_001387777.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475

Variant links:

Genes affected

TNS1 (HGNC:11973): (tensin 1) The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

TNS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4227002E-6).

BP6

Variant 2-217809974-C-T is Benign according to our data. Variant chr2-217809974-C-T is described in ClinVar as [Benign]. Clinvar id is 3060255.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1 linkuse as main transcript	c.5122G>A	p.Val1708Ile	missense_variant	30/33	ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1 linkuse as main transcript	c.5122G>A	p.Val1708Ile	missense_variant	30/33		NM_001387777.1	P2	Q9HBL0-3

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97663

AN:

151844

Hom.:

32073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.595

AC:

149216

AN:

250916

Hom.:

45044

AF XY:

0.586

AC XY:

79483

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.673

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.596

AC:

870372

AN:

1461230

Hom.:

261486

Cov.:

AF XY:

0.592

AC XY:

430324

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.630

Gnomad4 ASJ exome

AF:

0.668

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.480

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.643

AC:

97773

AN:

151962

Hom.:

32124

Cov.:

AF XY:

0.638

AC XY:

47414

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.635

Gnomad4 ASJ

AF:

0.670

Gnomad4 EAS

AF:

0.505

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.613

Hom.:

58685

Bravo

AF:

0.659

TwinsUK

AF:

0.606

AC:

2246

ALSPAC

AF:

0.615

AC:

2369

ESP6500AA

AF:

0.768

AC:

3386

ESP6500EA

AF:

0.611

AC:

5251

ExAC

AF:

0.595

AC:

72180

Asia WGS

AF:

0.515

AC:

1792

AN:

3478

EpiCase

AF:

0.616

EpiControl

AF:

0.611

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TNS1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.59

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.67

T;T;T;T;T;.;T

MetaRNN

Benign

0.0000024

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

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.61

Polyphen

0.0

.;B;.;B;.;B;B

Vest4

0.058, 0.11, 0.029, 0.047, 0.075, 0.077

MPC

0.099

ClinPred

0.0084

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.10

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