rs2104772

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002160.4(TNC):c.5029A>T(p.Ile1677Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,613,834 control chromosomes in the GnomAD database, including 153,510 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17242 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136268 hom. )

Consequence

TNC
NM_002160.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.850

Publications

71 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5833974E-4).

BP6

Variant 9-115046506-T-A is Benign according to our data. Variant chr9-115046506-T-A is described in ClinVar as Benign. ClinVar VariationId is 1238979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.5029A>T	p.Ile1677Leu	missense_variant	Exon 17 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.5029A>T	p.Ile1677Leu	missense_variant	Exon 17 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71588

AN:

151890

Hom.:

17222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.467

GnomAD2 exomes

AF:

0.437

AC:

109906

AN:

251412

AF XY:

0.433

show subpopulations

Gnomad AFR exome

AF:

0.561

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.444

GnomAD4 exome

AF:

0.430

AC:

628402

AN:

1461826

Hom.:

136268

Cov.:

AF XY:

0.429

AC XY:

312093

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.560

AC:

18742

AN:

33474

American (AMR)

AF:

0.425

AC:

18989

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10804

AN:

26136

East Asian (EAS)

AF:

0.450

AC:

17866

AN:

39700

South Asian (SAS)

AF:

0.406

AC:

35028

AN:

86256

European-Finnish (FIN)

AF:

0.470

AC:

25099

AN:

53418

Middle Eastern (MID)

AF:

0.482

AC:

2780

AN:

5768

European-Non Finnish (NFE)

AF:

0.425

AC:

472742

AN:

1111962

Other (OTH)

AF:

0.436

AC:

26352

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

23581

47162

70742

94323

117904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14492

28984

43476

57968

72460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.471

AC:

71644

AN:

152008

Hom.:

17242

Cov.:

AF XY:

0.472

AC XY:

35076

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.560

AC:

23192

AN:

41434

American (AMR)

AF:

0.441

AC:

6745

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1467

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2237

AN:

5166

South Asian (SAS)

AF:

0.400

AC:

1923

AN:

4810

European-Finnish (FIN)

AF:

0.483

AC:

5101

AN:

10570

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29362

AN:

67964

Other (OTH)

AF:

0.466

AC:

982

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1911

3821

5732

7642

9553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.436

Hom.:

11283

Bravo

AF:

0.474

TwinsUK

AF:

0.407

AC:

1510

ALSPAC

AF:

0.420

AC:

1619

ESP6500AA

AF:

0.563

AC:

2482

ESP6500EA

AF:

0.431

AC:

3705

ExAC

AF:

0.438

AC:

53222

Asia WGS

AF:

0.431

AC:

1504

AN:

3478

EpiCase

AF:

0.436

EpiControl

AF:

0.438

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 16115819) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Sep 10, 2021

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

0.26

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.14

.;T;.;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

T;T;T;.

MetaRNN

Benign

0.00016

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

.;L;.;.

PhyloP100

0.85

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

.;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.42

.;T;T;T

Sift4G

Benign

0.76

T;T;T;T

Polyphen

0.0040

.;B;.;.

Vest4

0.26

MutPred

0.44

.;Gain of disorder (P = 0.0919);.;.;

MPC

0.22

ClinPred

0.0071

GERP RS

3.4

Varity_R

0.19

gMVP

0.69

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over