9-115073620-C-T

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.3197G>A(p.Arg1066His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,578 control chromosomes in the GnomAD database, including 17,186 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1066C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.14 ( 1495 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15691 hom. )

Consequence

TNC
NM_002160.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.658

Publications

32 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:

LOC124902256 (HGNC:):

LOC124902256 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=0.0014590621).

BP6

Variant 9-115073620-C-T is Benign according to our data. Variant chr9-115073620-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.3197G>A	p.Arg1066His	missense_variant	Exon 10 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.3197G>A	p.Arg1066His	missense_variant	Exon 10 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20649

AN:

152004

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.0884

Gnomad ASJ

AF:

0.0695

Gnomad EAS

AF:

0.0625

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.122

AC:

30360

AN:

249366

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.0552

Gnomad EAS exome

AF:

0.0677

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.142

AC:

207994

AN:

1461456

Hom.:

15691

Cov.:

AF XY:

0.142

AC XY:

103229

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.132

AC:

4429

AN:

33468

American (AMR)

AF:

0.0562

AC:

2511

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0586

AC:

1528

AN:

26082

East Asian (EAS)

AF:

0.0449

AC:

1782

AN:

39688

South Asian (SAS)

AF:

0.118

AC:

10204

AN:

86240

European-Finnish (FIN)

AF:

0.156

AC:

8334

AN:

53408

Middle Eastern (MID)

AF:

0.0899

AC:

518

AN:

5762

European-Non Finnish (NFE)

AF:

0.154

AC:

170758

AN:

1111706

Other (OTH)

AF:

0.131

AC:

7930

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9722

19443

29165

38886

48608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6008

12016

18024

24032

30040

<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:

0.136

AC:

20659

AN:

152122

Hom.:

1495

Cov.:

AF XY:

0.133

AC XY:

9916

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.133

AC:

5508

AN:

41502

American (AMR)

AF:

0.0883

AC:

1350

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0695

AC:

241

AN:

3470

East Asian (EAS)

AF:

0.0624

AC:

323

AN:

5176

South Asian (SAS)

AF:

0.113

AC:

546

AN:

4818

European-Finnish (FIN)

AF:

0.149

AC:

1572

AN:

10562

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10602

AN:

67986

Other (OTH)

AF:

0.114

AC:

242

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

930

1860

2790

3720

4650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.136

Hom.:

3186

Bravo

AF:

0.129

TwinsUK

AF:

0.143

AC:

529

ALSPAC

AF:

0.157

AC:

604

ESP6500AA

AF:

0.128

AC:

566

ESP6500EA

AF:

0.145

AC:

1243

ExAC

AF:

0.126

AC:

15334

Asia WGS

AF:

0.0960

AC:

331

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 14, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.32

.;T;.;T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.68

T;T;T;T;T;.

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L;.;.;L;.

PhyloP100

0.66

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Uncertain

0.042

D;D;D;D;D;D

Polyphen

0.0010, 0.025

.;B;.;B;.;.

Vest4

0.087

MPC

0.20

ClinPred

0.0095

GERP RS

3.0

Varity_R

0.074

gMVP

0.44

Mutation Taster

=100/0

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