rs2274750

Variant names:

Variant summary

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

The NM_002160.4(TNC):c.5341G>A(p.Ala1781Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,834 control chromosomes in the GnomAD database, including 1,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 338 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1556 hom. )

Consequence

TNC
NM_002160.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

TNC (HGNC:5318): (tenascin C) This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

TNC links:

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

DELEC1 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=0.0016574562).

BP6

Variant 9-115040992-C-T is Benign according to our data. Variant chr9-115040992-C-T is described in ClinVar as [Benign]. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.5341G>A	p.Ala1781Thr	missense_variant	Exon 19 of 28	ENST00000350763.9	NP_002151.2	P24821-1Q4LE33B4E1W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9 link	c.5341G>A	p.Ala1781Thr	missense_variant	Exon 19 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8487

AN:

151950

Hom.:

339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0947

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0586

GnomAD3 exomes

AF:

0.0554

AC:

13933

AN:

251304

Hom.:

642

AF XY:

0.0493

AC XY:

6699

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0834

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.0256

Gnomad EAS exome

AF:

0.100

Gnomad SAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0292

Gnomad OTH exome

AF:

0.0450

GnomAD4 exome

AF:

0.0372

AC:

54402

AN:

1461766

Hom.:

1556

Cov.:

AF XY:

0.0362

AC XY:

26351

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0872

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0959

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.0761

Gnomad4 NFE exome

AF:

0.0291

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0559

AC:

8506

AN:

152068

Hom.:

338

Cov.:

AF XY:

0.0572

AC XY:

4256

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0807

Gnomad4 AMR

AF:

0.0951

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0759

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.0613

Alfa

AF:

0.0360

Hom.:

303

Bravo

AF:

0.0601

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.0908

AC:

400

ESP6500EA

AF:

0.0309

AC:

266

ExAC

AF:

0.0515

AC:

6255

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16741161) -

May 24, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D;D;D;D;.

MetaRNN

Benign

0.0017

T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

.;M;.;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

.;N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.17

.;T;D;D;D;D

Sift4G

Benign

0.066

T;D;T;T;T;T

Polyphen

0.95, 0.99

.;P;.;D;.;.

Vest4

0.30

MPC

0.49

ClinPred

0.030

GERP RS

4.1

Varity_R

0.19

gMVP

0.75

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