rs12347433

Variant names:

• chr9-115035318-T-C
• rs12347433
• NM_002160.4:c.5673A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_002160.4(TNC):​c.5673A>G​(p.Arg1891Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,611,976 control chromosomes in the GnomAD database, including 54,366 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3656 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50710 hom.)
• Consequence: TNC NM_002160.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.05
• Publications: 22 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 -17 ACMG points.

• BP6: Variant 9-115035318-T-C is Benign according to our data. Variant chr9-115035318-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5673A>G	p.Arg1891Arg	synonymous_variant	Exon 22 of 28	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5673A>G	p.Arg1891Arg	synonymous_variant	Exon 22 of 28	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31214 AN: 152000 Hom.: 3657 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.227 AC: 56401 AN: 248602 AF XY: 0.229

Gnomad AFR exome AF: 0.0858

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.258 AC: 376242 AN: 1459858 Hom.: 50710 Cov.: 33 AF XY: 0.255 AC XY: 185075 AN XY: 726258

African (AFR) AF: 0.0814 AC: 2715 AN: 33350

American (AMR) AF: 0.192 AC: 8564 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4078 AN: 26078

East Asian (EAS) AF: 0.143 AC: 5674 AN: 39558

South Asian (SAS) AF: 0.161 AC: 13829 AN: 85928

European-Finnish (FIN) AF: 0.279 AC: 14909 AN: 53388

Middle Eastern (MID) AF: 0.199 AC: 1142 AN: 5752

European-Non Finnish (NFE) AF: 0.280 AC: 311462 AN: 1110986

Other (OTH) AF: 0.230 AC: 13869 AN: 60308

GnomAD4 genome AF: 0.205 AC: 31212 AN: 152118 Hom.: 3656 Cov.: 32 AF XY: 0.202 AC XY: 15015 AN XY: 74342

African (AFR) AF: 0.0904 AC: 3751 AN: 41514

American (AMR) AF: 0.202 AC: 3081 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5172

South Asian (SAS) AF: 0.157 AC: 756 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2801 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18811 AN: 67972

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.252 Hom.: 19023

Bravo AF: 0.198

Asia WGS AF: 0.154 AC: 535 AN: 3478

EpiCase AF: 0.273

EpiControl AF: 0.272

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12347433; hg19: chr9-117797597; COSMIC: COSV60780714; COSMIC: COSV60780714;