Variant 2-217804565-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001387777.1(TNS1):c.5414C>T(p.Thr1805Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,614,146 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0037 ( 14 hom. )

Consequence

TNS1
NM_001387777.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.78

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012797296).

BP6

Variant 2-217804565-G-A is Benign according to our data. Variant chr2-217804565-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 363 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1 linkuse as main transcript	c.5414C>T	p.Thr1805Met	missense_variant	33/33	ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1 linkuse as main transcript	c.5414C>T	p.Thr1805Met	missense_variant	33/33		NM_001387777.1	P2	Q9HBL0-3

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00393

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00252

AC:

630

AN:

250420

Hom.:

AF XY:

0.00256

AC XY:

347

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00434

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00370

AC:

5406

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2673

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.00438

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152318

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00206

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00273

AC:

332

EpiCase

AF:

0.00354

EpiControl

AF:

0.00415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TNS1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 14, 2022

This variant is classified as likely 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

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.039

MetaRNN

Benign

0.013

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

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

Polyphen

1.0, 1.0

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

Vest4

0.45, 0.55, 0.46, 0.45, 0.44, 0.43

MVP

0.39

MPC

0.57

ClinPred

0.025

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.57

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