9-115059339-A-C

Variant names:

• chr9-115059339-A-C
• rs1060545
• NM_002160.4:c.4306+391T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002160.4(TNC):​c.4306+391T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,966 control chromosomes in the GnomAD database, including 20,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20966 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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.4306+391T>G		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.4306+391T>G		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.4306+391T>G		intron	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.4306+391T>G		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.4306+391T>G		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.3215-1914T>G		intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78333 AN: 151848 Hom.: 20939 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78407 AN: 151966 Hom.: 20966 Cov.: 32 AF XY: 0.511 AC XY: 37920 AN XY: 74244

African (AFR) AF: 0.647 AC: 26820 AN: 41436

American (AMR) AF: 0.388 AC: 5925 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5162

South Asian (SAS) AF: 0.359 AC: 1730 AN: 4820

European-Finnish (FIN) AF: 0.520 AC: 5478 AN: 10534

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33777 AN: 67942

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.479 Hom.: 11394

Bravo AF: 0.509

Asia WGS AF: 0.353 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.69
PromoterAI		-0.017	Neutral
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: rs1060545; hg19: chr9-117821618;