9-115021283-AAGAGAGAG-AAGAGAGAGAG

Variant names:

• chr9-115021283-A-AAG
• rs766737426
• NM_002160.4:c.6496-18_6496-17dupCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002160.4(TNC):​c.6496-18_6496-17dupCT variant causes a intron change. The variant allele was found at a frequency of 0.00388 in 1,095,144 control chromosomes in the GnomAD database, including 25 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0089 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (2 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00889 (1331/149700) while in subpopulation AFR AF= 0.0289 (1178/40778). AF 95% confidence interval is 0.0275. There are 23 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.6496-18_6496-17dupCT		intron_variant	Intron 27 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.6496-17_6496-16insCT		intron_variant	Intron 27 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1328 AN: 149594 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00240

Gnomad ASJ AF: 0.00754

Gnomad EAS AF: 0.00604

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000535

Gnomad OTH AF: 0.00685

GnomAD3 exomes AF: 0.00408 AC: 747 AN: 182926 Hom.: 1 AF XY: 0.00345 AC XY: 343 AN XY: 99294

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.00561

Gnomad EAS exome AF: 0.00493

Gnomad SAS exome AF: 0.00305

Gnomad FIN exome AF: 0.000602

Gnomad NFE exome AF: 0.000983

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00309 AC: 2920 AN: 945444 Hom.: 2 Cov.: 22 AF XY: 0.00302 AC XY: 1420 AN XY: 470866

Gnomad4 AFR exome AF: 0.0322

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00808

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.00289

Gnomad4 FIN exome AF: 0.000256

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00394

GnomAD4 genome AF: 0.00889 AC: 1331 AN: 149700 Hom.: 23 Cov.: 32 AF XY: 0.00854 AC XY: 624 AN XY: 73048

Gnomad4 AFR AF: 0.0289

Gnomad4 AMR AF: 0.00240

Gnomad4 ASJ AF: 0.00754

Gnomad4 EAS AF: 0.00605

Gnomad4 SAS AF: 0.00213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000535

Gnomad4 OTH AF: 0.00678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs766737426; hg19: chr9-117783562;