Variant rs3748172 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.3165C>T(p.Ala1055=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,102 control chromosomes in the GnomAD database, including 852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 114 hom., cov: 32)

Exomes 𝑓: 0.012 ( 738 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-115073652-G-A is Benign according to our data. Variant chr9-115073652-G-A is described in ClinVar as [Benign]. Clinvar id is 586834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4 linkuse as main transcript	c.3165C>T	p.Ala1055=	synonymous_variant	10/28	ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9 linkuse as main transcript	c.3165C>T	p.Ala1055=	synonymous_variant	10/28	1	NM_002160.4	P1	P24821-1
DELEC1	ENST00000649121.1 linkuse as main transcript	n.79-10603G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2479

AN:

152116

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0792

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00218

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.0333

AC:

8344

AN:

250572

Hom.:

440

AF XY:

0.0311

AC XY:

4216

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.0556

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0117

AC:

17166

AN:

1461868

Hom.:

738

Cov.:

AF XY:

0.0127

AC XY:

9215

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.0964

Gnomad4 SAS exome

AF:

0.0559

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0164

AC:

2490

AN:

152234

Hom.:

114

Cov.:

AF XY:

0.0198

AC XY:

1472

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.0796

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0633

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.00833

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00184

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	clinical testing	GeneDx	Dec 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 10, 2018	- -

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.38

DANN

Benign

0.42

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

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