9-115086115-T-C

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.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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.93 ( 65484 hom., cov: 35)

Exomes 𝑓: 0.94 ( 651039 hom. )

Consequence

TNC
NM_002160.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0600

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=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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.1616A>G	p.Gln539Arg	missense_variant	Exon 3 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.1616A>G	p.Gln539Arg	missense_variant	Exon 3 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

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

GnomAD3 exomes

AF:

0.951

AC:

238665

AN:

251018

Hom.:

113599

AF XY:

0.952

AC XY:

129145

AN XY:

135696

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 SAS exome

AF:

0.972

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

Gnomad4 AFR exome

AF:

0.874

Gnomad4 AMR exome

AF:

0.958

Gnomad4 ASJ exome

AF:

0.927

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.972

Gnomad4 FIN exome

AF:

0.980

Gnomad4 NFE exome

AF:

0.940

Gnomad4 OTH exome

AF:

0.940

GnomAD4 genome

AF:

0.926

AC:

141078

AN:

152272

Hom.:

65484

Cov.:

AF XY:

0.930

AC XY:

69258

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.875

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.931

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.976

Gnomad4 FIN

AF:

0.982

Gnomad4 NFE

AF:

0.937

Gnomad4 OTH

AF:

0.931

Alfa

AF:

0.934

Hom.:

162379

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

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

- -

Nov 12, 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

0.065

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.021

DANN

Benign

0.13

DEOGEN2

Benign

0.14

.;T;.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.11

T;T;T;T;T;.

MetaRNN

Benign

0.0000029

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.0

.;N;.;.;N;.

PrimateAI

Benign

0.19

PROVEAN

Benign

1.3

N;N;N;N;N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0, 0.0010

.;B;.;B;.;.

Vest4

0.071

MPC

0.17

ClinPred

0.0021

GERP RS

0.11

Varity_R

0.049

gMVP

0.63

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