9-115021272-TAAAA-TAAAAA

Variant names:

• chr9-115021272-T-TA
• rs5900112
• NM_002160.4:c.6496-6dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002160.4(TNC):​c.6496-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,304,716 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 24)
  • Exomes 𝑓: 0.013 (1 hom.)
• Consequence: TNC NM_002160.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 400 AD gene.

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.6496-6dupT		splice_region intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.7045-6dupT		splice_region intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.7045-6dupT		splice_region 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.6496-6dupT		splice_region intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5677-6dupT		splice_region intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5407-6dupT		splice_region intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 398 AN: 144338 Hom.: 2 Cov.: 24

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.000603

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.000542

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.00359

GnomAD2 exomes AF: 0.00994 AC: 1610 AN: 161918 AF XY: 0.00966

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.0110

Gnomad FIN exome AF: 0.00659

Gnomad NFE exome AF: 0.00651

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.0131 AC: 15173 AN: 1160304 Hom.: 1 Cov.: 0 AF XY: 0.0127 AC XY: 7360 AN XY: 577374

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0257 AC: 610 AN: 23772

American (AMR) AF: 0.0138 AC: 442 AN: 31930

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 243 AN: 19172

East Asian (EAS) AF: 0.00926 AC: 278 AN: 30012

South Asian (SAS) AF: 0.0198 AC: 1244 AN: 62864

European-Finnish (FIN) AF: 0.00632 AC: 269 AN: 42536

Middle Eastern (MID) AF: 0.00939 AC: 40 AN: 4262

European-Non Finnish (NFE) AF: 0.0127 AC: 11420 AN: 898652

Other (OTH) AF: 0.0133 AC: 627 AN: 47104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00277 AC: 400 AN: 144412 Hom.: 2 Cov.: 24 AF XY: 0.00289 AC XY: 202 AN XY: 70016

African (AFR) AF: 0.00572 AC: 222 AN: 38792

American (AMR) AF: 0.00138 AC: 20 AN: 14514

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3372

East Asian (EAS) AF: 0.000605 AC: 3 AN: 4962

South Asian (SAS) AF: 0.00601 AC: 27 AN: 4496

European-Finnish (FIN) AF: 0.000542 AC: 5 AN: 9226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00174 AC: 115 AN: 65918

Other (OTH) AF: 0.00356 AC: 7 AN: 1966

Alfa AF: 0.0121 Hom.: 178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29
Mutation Taster		=99/1	polymorphism

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: rs5900112; hg19: chr9-117783551;