Genetic Variant TNC:p.Gly2048Gly (chr9-115029385-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002160.4(TNC):c.6144G>A(p.Gly2048Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,002 control chromosomes in the GnomAD database, including 793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 120 hom., cov: 32)

Exomes 𝑓: 0.011 ( 673 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.549

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 9-115029385-C-T is Benign according to our data. Variant chr9-115029385-C-T is described in ClinVar as [Benign]. Clinvar id is 586836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.549 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.6144G>A	p.Gly2048Gly	synonymous_variant	Exon 25 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.6144G>A	p.Gly2048Gly	synonymous_variant	Exon 25 of 28	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2575

AN:

152044

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0896

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0518

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0322

AC:

8097

AN:

251320

Hom.:

425

AF XY:

0.0294

AC XY:

3999

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.0452

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.0111

AC:

16209

AN:

1461840

Hom.:

673

Cov.:

AF XY:

0.0117

AC XY:

8493

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.0455

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0170

AC:

2586

AN:

152162

Hom.:

120

Cov.:

AF XY:

0.0206

AC XY:

1530

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.0900

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.0525

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.0223

Asia WGS

AF:

0.0620

AC:

215

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 10, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 12, 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

- -

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Mar 15, 2022

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

BayesDel_noAF

Benign

-0.25

CADD

Benign

7.3

DANN

Benign

0.67

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