chr9-115086115-T-C

Variant names:

Variant summary

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

The NM_001439065.1(TNC):c.1616A>G(p.Gln539Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 1,614,142 control chromosomes in the GnomAD database, including 716,523 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 0.93 ( 65484 hom., cov: 35)

Exomes 𝑓: 0.94 ( 651039 hom. )

Consequence

TNC
NM_001439065.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0600

Publications

41 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=2.8961022E-6).

BP6

Variant 9-115086115-T-C is Benign according to our data. Variant chr9-115086115-T-C is described in ClinVar as Benign. ClinVar VariationId is 1259178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439065.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	NM_002160.4	MANE Select	c.1616A>G	p.Gln539Arg	missense	Exon 3 of 28	NP_002151.2
TNC	NM_001439065.1		c.1616A>G	p.Gln539Arg	missense	Exon 3 of 30	NP_001425994.1
TNC	NM_001439066.1		c.1616A>G	p.Gln539Arg	missense	Exon 4 of 31	NP_001425995.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	ENST00000350763.9	TSL:1 MANE Select	c.1616A>G	p.Gln539Arg	missense	Exon 3 of 28	ENSP00000265131.4
TNC	ENST00000423613.6	TSL:1	c.1616A>G	p.Gln539Arg	missense	Exon 3 of 25	ENSP00000411406.2
TNC	ENST00000542877.6	TSL:1	c.1616A>G	p.Gln539Arg	missense	Exon 3 of 24	ENSP00000442242.1

Frequencies

GnomAD3 genomes

AF:

0.927

AC:

140971

AN:

152154

Hom.:

65432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.905

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.931

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.976

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.937

Gnomad OTH

AF:

0.931

GnomAD2 exomes

AF:

0.951

AC:

238665

AN:

251018

AF XY:

0.952

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.981

Gnomad NFE exome

AF:

0.942

Gnomad OTH exome

AF:

0.944

GnomAD4 exome

AF:

0.943

AC:

1379243

AN:

1461870

Hom.:

651039

Cov.:

AF XY:

0.944

AC XY:

686646

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.874

AC:

29257

AN:

33480

American (AMR)

AF:

0.958

AC:

42848

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.927

AC:

24216

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39700

South Asian (SAS)

AF:

0.972

AC:

83822

AN:

86258

European-Finnish (FIN)

AF:

0.980

AC:

52329

AN:

53402

Middle Eastern (MID)

AF:

0.893

AC:

5153

AN:

5768

European-Non Finnish (NFE)

AF:

0.940

AC:

1045144

AN:

1112008

Other (OTH)

AF:

0.940

AC:

56783

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

5435

10870

16304

21739

27174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21584

43168

64752

86336

107920

<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:

0.926

AC:

141078

AN:

152272

Hom.:

65484

Cov.:

AF XY:

0.930

AC XY:

69258

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.875

AC:

36345

AN:

41552

American (AMR)

AF:

0.942

AC:

14401

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.931

AC:

3229

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5173

AN:

5180

South Asian (SAS)

AF:

0.976

AC:

4710

AN:

4826

European-Finnish (FIN)

AF:

0.982

AC:

10429

AN:

10622

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.937

AC:

63754

AN:

68008

Other (OTH)

AF:

0.931

AC:

1969

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

542

1083

1625

2166

2708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.932

Hom.:

222619

Bravo

AF:

0.921

TwinsUK

AF:

0.941

AC:

3490

ALSPAC

AF:

0.941

AC:

3627

ESP6500AA

AF:

0.878

AC:

3870

ESP6500EA

AF:

0.932

AC:

8014

ExAC

AF:

0.951

AC:

115428

Asia WGS

AF:

0.970

AC:

3372

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autosomal dominant nonsyndromic hearing loss 56 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.021

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.14

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000029

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.0

PhyloP100

0.060

PrimateAI

Benign

0.19

PROVEAN

Benign

1.3

REVEL

Benign

0.046

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MPC

0.17

ClinPred

0.0021

GERP RS

0.11

Varity_R

0.049

gMVP

0.63

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over