rs13321

Variant names:

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.6022G>C(p.Glu2008Gln) variant causes a missense change. The variant allele was found at a frequency of 0.707 in 1,613,310 control chromosomes in the GnomAD database, including 404,310 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38313 hom., cov: 32)

Exomes 𝑓: 0.71 ( 365997 hom. )

Consequence

TNC
NM_002160.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.44

Publications

57 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=7.3580927E-6).

BP6

Variant 9-115030304-C-G is Benign according to our data. Variant chr9-115030304-C-G is described in ClinVar as Benign. ClinVar VariationId is 1259794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.6022G>C	p.Glu2008Gln	missense_variant	Exon 24 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.6022G>C	p.Glu2008Gln	missense_variant	Exon 24 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.708

AC:

107631

AN:

151972

Hom.:

38263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.709

GnomAD2 exomes

AF:

0.682

AC:

171202

AN:

250990

AF XY:

0.680

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.640

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.723

Gnomad NFE exome

AF:

0.718

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.707

AC:

1032366

AN:

1461220

Hom.:

365997

Cov.:

AF XY:

0.705

AC XY:

512219

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.739

AC:

24731

AN:

33464

American (AMR)

AF:

0.649

AC:

29005

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

16224

AN:

26124

East Asian (EAS)

AF:

0.551

AC:

21876

AN:

39692

South Asian (SAS)

AF:

0.642

AC:

55336

AN:

86210

European-Finnish (FIN)

AF:

0.729

AC:

38918

AN:

53412

Middle Eastern (MID)

AF:

0.677

AC:

3898

AN:

5760

European-Non Finnish (NFE)

AF:

0.720

AC:

800482

AN:

1111478

Other (OTH)

AF:

0.694

AC:

41896

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14958

29916

44873

59831

74789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19918

39836

59754

79672

99590

<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:

0.708

AC:

107731

AN:

152090

Hom.:

38313

Cov.:

AF XY:

0.706

AC XY:

52520

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.735

AC:

30507

AN:

41506

American (AMR)

AF:

0.683

AC:

10447

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2143

AN:

3470

East Asian (EAS)

AF:

0.554

AC:

2850

AN:

5148

South Asian (SAS)

AF:

0.634

AC:

3049

AN:

4808

European-Finnish (FIN)

AF:

0.718

AC:

7598

AN:

10580

Middle Eastern (MID)

AF:

0.675

AC:

197

AN:

292

European-Non Finnish (NFE)

AF:

0.717

AC:

48702

AN:

67970

Other (OTH)

AF:

0.711

AC:

1502

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1612

3224

4835

6447

8059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.706

Hom.:

28739

Bravo

AF:

0.704

TwinsUK

AF:

0.713

AC:

2645

ALSPAC

AF:

0.713

AC:

2748

ESP6500AA

AF:

0.735

AC:

3238

ESP6500EA

AF:

0.705

AC:

6061

ExAC

AF:

0.685

AC:

83191

Asia WGS

AF:

0.632

AC:

2197

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.059

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.067

.;T;.;T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.031

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.12

T;T;T;T;T;.

MetaRNN

Benign

0.0000074

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

.;N;.;.;.;.

PhyloP100

6.4

PrimateAI

Benign

0.42

PROVEAN

Benign

1.8

.;N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

1.0

.;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0, 0.043

.;B;.;B;.;.

Vest4

0.083

MPC

0.15

ClinPred

0.012

GERP RS

5.3

Varity_R

0.26

gMVP

0.48

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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