Variant rs2992147 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002160.4(TNC):c.696A>G(p.Val232Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,822 control chromosomes in the GnomAD database, including 158,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17667 hom., cov: 34)

Exomes 𝑓: 0.44 ( 140852 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.850

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:):

DELEC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-115087035-T-C is Benign according to our data. Variant chr9-115087035-T-C is described in ClinVar as [Benign]. Clinvar id is 1280191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115087035-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4 linkuse as main transcript	c.696A>G	p.Val232Val	synonymous_variant	3/28	ENST00000350763.9	NP_002151.2	P24821-1Q4LE33B4E1W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9 linkuse as main transcript	c.696A>G	p.Val232Val	synonymous_variant	3/28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72248

AN:

151882

Hom.:

17625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.447

AC:

112281

AN:

251240

Hom.:

26041

AF XY:

0.440

AC XY:

59792

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.578

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.436

AC:

637220

AN:

1461822

Hom.:

140852

Cov.:

AF XY:

0.434

AC XY:

315259

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.584

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.432

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.476

AC:

72354

AN:

152000

Hom.:

17667

Cov.:

AF XY:

0.474

AC XY:

35264

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.459

Hom.:

8881

Bravo

AF:

0.488

Asia WGS

AF:

0.395

AC:

1377

AN:

3478

EpiCase

AF:

0.437

EpiControl

AF:

0.444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2018	- -

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

DANN

Benign

0.34

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