rs13321

chr9-115030304-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):c.6022G>C(p.Glu2008Gln) variant causes a missense change. The variant allele was found at a frequency of 0.707 in 1,613,310 control chromosomes in the GnomAD database, including 404,310 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.71 (38313 hom., cov: 32)
  • Exomes 𝑓: 0.71 (365997 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.44

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.3580927E-6).
• BP6: Variant 9-115030304-C-G is Benign according to our data. Variant chr9-115030304-C-G is described in ClinVar as [Benign]. Clinvar id is 1259794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.6022G>C	p.Glu2008Gln	missense_variant	24/28	ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.6022G>C	p.Glu2008Gln	missense_variant	24/28	1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-53951C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107631 AN: 151972 Hom.: 38263 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.709

GnomAD3 exomes AF: 0.682 AC: 171202 AN: 250990 Hom.: 58974 AF XY: 0.680 AC XY: 92255 AN XY: 135634

Gnomad AFR exome AF: 0.726

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.640

Gnomad FIN exome AF: 0.723

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.688

GnomAD4 exome AF: 0.707 AC: 1032366 AN: 1461220 Hom.: 365997 Cov.: 50 AF XY: 0.705 AC XY: 512219 AN XY: 726846

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.708 AC: 107731 AN: 152090 Hom.: 38313 Cov.: 32 AF XY: 0.706 AC XY: 52520 AN XY: 74352

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.711

Alfa AF: 0.706 Hom.: 28739

Bravo AF: 0.704

TwinsUK AF: 0.713 AC: 2645

ALSPAC AF: 0.713 AC: 2748

ESP6500AA AF: 0.735 AC: 3238

ESP6500EA AF: 0.705 AC: 6061

ExAC AF: 0.685 AC: 83191

Asia WGS AF: 0.632 AC: 2197 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 56 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	17
Dann	Benign	0.23
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.031
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.12	T;T;T;T;T;.
MetaRNN	Benign	0.0000074	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.42	T
REVEL	Benign	0.27
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0, 0.043	.;B;.;B;.;.
Vest4		0.083
MPC		0.15
ClinPred		0.012	T
GERP RS		5.3
Varity_R		0.26
gMVP		0.48

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

Other links and lift over

dbSNP: rs13321; hg19: chr9-117792583; COSMIC: COSV60785451;