NM_002160.4:c.5126-674C>T

Variant names:

• chr9-115043015-G-A
• rs10759753
• NM_002160.4:c.5126-674C>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.5126-674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,092 control chromosomes in the GnomAD database, including 47,229 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 0.78 (47229 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• 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 = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5126-674C>T		intron_variant	Intron 17 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5126-674C>T		intron_variant	Intron 17 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118956 AN: 151974 Hom.: 47163 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.783 AC: 119081 AN: 152092 Hom.: 47229 Cov.: 31 AF XY: 0.783 AC XY: 58183 AN XY: 74348

African (AFR) AF: 0.916 AC: 38016 AN: 41486

American (AMR) AF: 0.735 AC: 11237 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2534 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2975 AN: 5142

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4820

European-Finnish (FIN) AF: 0.793 AC: 8387 AN: 10582

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50099 AN: 67992

Other (OTH) AF: 0.784 AC: 1655 AN: 2112

Alfa AF: 0.771 Hom.: 5617

Bravo AF: 0.784

Asia WGS AF: 0.644 AC: 2244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.69
PhyloP100		-0.72
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: rs10759753; hg19: chr9-117805294;