Variant 12-53049172-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000314276.7(TNS2):c.29G>C(p.Arg10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,581,972 control chromosomes in the GnomAD database, including 351,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 24843 hom., cov: 32)

Exomes 𝑓: 0.66 ( 326391 hom. )

Consequence

TNS2
ENST00000314276.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

TNS2 (HGNC:19737): (tensin 2) The protein encoded by this gene belongs to the tensin family. Tensin is a focal adhesion molecule that binds to actin filaments and participates in signaling pathways. This protein plays a role in regulating cell migration. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

TNS2 links:

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

TNS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.5551361E-6).

BP6

Variant 12-53049172-G-C is Benign according to our data. Variant chr12-53049172-G-C is described in ClinVar as [Benign]. Clinvar id is 1244109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNS2-AS1	NR_033854.1 linkuse as main transcript	n.298-3111C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
TNS2	ENST00000314276.7 linkuse as main transcript	c.29G>C	p.Arg10Thr	missense_variant	1/29	1	ENSP00000319756	Q63HR2-4
TNS2	ENST00000379902.7 linkuse as main transcript	c.-298+2109G>C		intron_variant		1	ENSP00000369232	Q63HR2-5
TNS2-AS1	ENST00000546793.1 linkuse as main transcript	n.298-3111C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80543

AN:

151986

Hom.:

24835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.569

AC:

127441

AN:

224006

Hom.:

40712

AF XY:

0.584

AC XY:

71264

AN XY:

122078

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.651

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.527

Gnomad FIN exome

AF:

0.707

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.628

GnomAD4 exome

AF:

0.662

AC:

946606

AN:

1429868

Hom.:

326391

Cov.:

AF XY:

0.661

AC XY:

469378

AN XY:

710336

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.650

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.709

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.530

AC:

80581

AN:

152104

Hom.:

24843

Cov.:

AF XY:

0.526

AC XY:

39084

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.701

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.613

Hom.:

5626

Bravo

AF:

0.498

TwinsUK

AF:

0.714

AC:

2648

ALSPAC

AF:

0.707

AC:

2723

ESP6500AA

AF:

0.254

AC:

1120

ESP6500EA

AF:

0.700

AC:

6017

ExAC

AF:

0.564

AC:

68431

Asia WGS

AF:

0.323

AC:

1127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0000036

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.98

P;P

PROVEAN

Benign

-0.23

REVEL

Benign

0.18

Sift

Uncertain

0.021

Sift4G

Benign

0.42

Polyphen

0.13

Vest4

0.10

MPC

0.33

ClinPred

0.0081

GERP RS

2.8

gMVP

0.37

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