NM_002160.4:c.5202A>G

Variant names:

• chr9-115042265-T-C
• rs1061495
• NM_002160.4:c.5202A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002160.4(TNC):​c.5202A>G​(p.Thr1734Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,764 control chromosomes in the GnomAD database, including 56,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8182 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48807 hom.)
• Consequence: TNC NM_002160.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.120
• Publications: 31 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.018).
• BP6: Variant 9-115042265-T-C is Benign according to our data. Variant chr9-115042265-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.5202A>G	p.Thr1734Thr	synonymous	Exon 18 of 28	NP_002151.2
	TNC	NM_001439065.1		c.5751A>G	p.Thr1917Thr	synonymous	Exon 20 of 30	NP_001425994.1
	TNC	NM_001439066.1		c.5751A>G	p.Thr1917Thr	synonymous	Exon 21 of 31	NP_001425995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.5202A>G	p.Thr1734Thr	synonymous	Exon 18 of 28	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.4383A>G	p.Thr1461Thr	synonymous	Exon 15 of 25	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.4113A>G	p.Thr1371Thr	synonymous	Exon 14 of 24	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46907 AN: 152016 Hom.: 8172 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.242 AC: 60843 AN: 251276 AF XY: 0.233

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.251 AC: 367515 AN: 1461630 Hom.: 48807 Cov.: 33 AF XY: 0.246 AC XY: 178947 AN XY: 727120

African (AFR) AF: 0.483 AC: 16162 AN: 33474

American (AMR) AF: 0.247 AC: 11050 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5210 AN: 26132

East Asian (EAS) AF: 0.115 AC: 4548 AN: 39694

South Asian (SAS) AF: 0.113 AC: 9728 AN: 86234

European-Finnish (FIN) AF: 0.296 AC: 15794 AN: 53404

Middle Eastern (MID) AF: 0.200 AC: 1153 AN: 5766

European-Non Finnish (NFE) AF: 0.260 AC: 288939 AN: 1111836

Other (OTH) AF: 0.247 AC: 14931 AN: 60380

GnomAD4 genome AF: 0.309 AC: 46963 AN: 152134 Hom.: 8182 Cov.: 32 AF XY: 0.303 AC XY: 22513 AN XY: 74356

African (AFR) AF: 0.478 AC: 19847 AN: 41478

American (AMR) AF: 0.247 AC: 3777 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.138 AC: 717 AN: 5180

South Asian (SAS) AF: 0.117 AC: 565 AN: 4816

European-Finnish (FIN) AF: 0.280 AC: 2967 AN: 10598

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17533 AN: 67992

Other (OTH) AF: 0.268 AC: 563 AN: 2104

Alfa AF: 0.266 Hom.: 9188

Bravo AF: 0.315

Asia WGS AF: 0.137 AC: 479 AN: 3478

EpiCase AF: 0.250

EpiControl AF: 0.249

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.36
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs1061495; hg19: chr9-117804544; COSMIC: COSV60782508; COSMIC: COSV60782508;