NM_002160.4:c.5249-357C>T

Variant names:

• chr9-115041441-G-A
• rs10759752
• NM_002160.4:c.5249-357C>T

Variant summary

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

The NM_002160.4(TNC):​c.5249-357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,980 control chromosomes in the GnomAD database, including 24,396 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 0.56 (24396 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5249-357C>T		intron_variant	Intron 18 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5249-357C>T		intron_variant	Intron 18 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85159 AN: 151862 Hom.: 24380 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.561 AC: 85211 AN: 151980 Hom.: 24396 Cov.: 32 AF XY: 0.557 AC XY: 41395 AN XY: 74288

African (AFR) AF: 0.615 AC: 25483 AN: 41438

American (AMR) AF: 0.430 AC: 6570 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1827 AN: 5168

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4818

European-Finnish (FIN) AF: 0.597 AC: 6296 AN: 10548

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39298 AN: 67942

Other (OTH) AF: 0.521 AC: 1102 AN: 2116

Alfa AF: 0.561 Hom.: 30152

Bravo AF: 0.550

Asia WGS AF: 0.402 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.33
PhyloP100		0.41
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: rs10759752; hg19: chr9-117803720;