rs2274750

Variant names:

• chr9-115040992-C-T
• rs2274750
• NM_002160.4:c.5341G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.5341G>A​(p.Ala1781Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,834 control chromosomes in the GnomAD database, including 1,894 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (338 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1556 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.52
• Publications: 24 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016574562).
• BP6: Variant 9-115040992-C-T is Benign according to our data. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115040992-C-T is described in CliVar as Benign. Clinvar id is 586835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5341G>A	p.Ala1781Thr	missense_variant	Exon 19 of 28	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5341G>A	p.Ala1781Thr	missense_variant	Exon 19 of 28	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8487 AN: 151950 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0586

GnomAD2 exomes AF: 0.0554 AC: 13933 AN: 251304 AF XY: 0.0493

Gnomad AFR exome AF: 0.0834

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.100

Gnomad FIN exome AF: 0.0777

Gnomad NFE exome AF: 0.0292

Gnomad OTH exome AF: 0.0450

GnomAD4 exome AF: 0.0372 AC: 54402 AN: 1461766 Hom.: 1556 Cov.: 34 AF XY: 0.0362 AC XY: 26351 AN XY: 727190

African (AFR) AF: 0.0872 AC: 2919 AN: 33478

American (AMR) AF: 0.136 AC: 6065 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 656 AN: 26134

East Asian (EAS) AF: 0.0959 AC: 3807 AN: 39684

South Asian (SAS) AF: 0.0193 AC: 1662 AN: 86244

European-Finnish (FIN) AF: 0.0761 AC: 4065 AN: 53414

Middle Eastern (MID) AF: 0.0312 AC: 180 AN: 5768

European-Non Finnish (NFE) AF: 0.0291 AC: 32347 AN: 1111966

Other (OTH) AF: 0.0447 AC: 2701 AN: 60392

GnomAD4 genome AF: 0.0559 AC: 8506 AN: 152068 Hom.: 338 Cov.: 32 AF XY: 0.0572 AC XY: 4256 AN XY: 74356

African (AFR) AF: 0.0807 AC: 3345 AN: 41460

American (AMR) AF: 0.0951 AC: 1453 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.110 AC: 568 AN: 5148

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4820

European-Finnish (FIN) AF: 0.0759 AC: 803 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0294 AC: 1997 AN: 67998

Other (OTH) AF: 0.0613 AC: 129 AN: 2104

Alfa AF: 0.0381 Hom.: 641

Bravo AF: 0.0601

TwinsUK AF: 0.0291 AC: 108

ALSPAC AF: 0.0272 AC: 105

ESP6500AA AF: 0.0908 AC: 400

ESP6500EA AF: 0.0309 AC: 266

ExAC AF: 0.0515 AC: 6255

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 24, 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

This variant is associated with the following publications: (PMID: 16741161) -

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
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;.;T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;.
MetaRNN	Benign	0.0017	T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.5	.;M;.;.;.;.
PhyloP100		2.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	.;N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.17	.;T;D;D;D;D
Sift4G	Benign	0.066	T;D;T;T;T;T
Polyphen		0.95, 0.99	.;P;.;D;.;.
Vest4		0.30
MPC		0.49
ClinPred		0.030	T
GERP RS		4.1
Varity_R		0.19
gMVP		0.75
Mutation Taster		=59/41	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274750; hg19: chr9-117803271; COSMIC: COSV60782497;