chr9-115087035-T-C

Variant names:

• chr9-115087035-T-C
• rs2992147
• NM_002160.4:c.696A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.850
• 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 -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 VariationId is 1280191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.696A>G	p.Val232Val	synonymous	Exon 3 of 28	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.696A>G	p.Val232Val	synonymous	Exon 3 of 30	NP_001425994.1
	TNC	NM_001439066.1		c.696A>G	p.Val232Val	synonymous	Exon 4 of 31	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.696A>G	p.Val232Val	synonymous	Exon 3 of 28	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.696A>G	p.Val232Val	synonymous	Exon 3 of 25	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.696A>G	p.Val232Val	synonymous	Exon 3 of 24	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72248 AN: 151882 Hom.: 17625 Cov.: 34

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

GnomAD2 exomes AF: 0.447 AC: 112281 AN: 251240 AF XY: 0.440

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 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.: 84 AF XY: 0.434 AC XY: 315259 AN XY: 727214

African (AFR) AF: 0.584 AC: 19545 AN: 33480

American (AMR) AF: 0.573 AC: 25648 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 14355 AN: 26136

East Asian (EAS) AF: 0.293 AC: 11626 AN: 39698

South Asian (SAS) AF: 0.386 AC: 33336 AN: 86256

European-Finnish (FIN) AF: 0.438 AC: 23369 AN: 53372

Middle Eastern (MID) AF: 0.460 AC: 2651 AN: 5768

European-Non Finnish (NFE) AF: 0.432 AC: 480072 AN: 1111998

Other (OTH) AF: 0.441 AC: 26618 AN: 60392

GnomAD4 genome AF: 0.476 AC: 72354 AN: 152000 Hom.: 17667 Cov.: 34 AF XY: 0.474 AC XY: 35264 AN XY: 74334

African (AFR) AF: 0.574 AC: 23809 AN: 41480

American (AMR) AF: 0.536 AC: 8183 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1445 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1771 AN: 4814

European-Finnish (FIN) AF: 0.427 AC: 4513 AN: 10578

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29257 AN: 67918

Other (OTH) AF: 0.469 AC: 987 AN: 2104

Alfa AF: 0.458 Hom.: 13912

Bravo AF: 0.488

Asia WGS AF: 0.395 AC: 1377 AN: 3478

EpiCase AF: 0.437

EpiControl AF: 0.444

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 56 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.34
PhyloP100		-0.85
Mutation Taster		=98/2	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: rs2992147; hg19: chr9-117849314; COSMIC: COSV60782318; COSMIC: COSV60782318;