chr9-115021272-TA-T

Position:

• chr9-115021272-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002160.4(TNC):​c.6496-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 144,126 control chromosomes in the GnomAD database, including 3,540 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3540 hom., cov: 24)
  • Exomes 𝑓: 0.32 (7845 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNC NM_002160.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.292

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 -10 ACMG points.

• BP6: Variant 9-115021272-TA-T is Benign according to our data. Variant chr9-115021272-TA-T is described in ClinVar as [Benign]. Clinvar id is 1243437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4	c.6496-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.6496-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002160.4	ENSP00000265131	P1
DELEC1	ENST00000649121.1	n.78+51623del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.214 AC: 30892 AN: 144050 Hom.: 3541 Cov.: 24

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.218

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.317 AC: 344012 AN: 1085872 Hom.: 7845 Cov.: 0 AF XY: 0.315 AC XY: 169838 AN XY: 538568

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.214 AC: 30889 AN: 144126 Hom.: 3540 Cov.: 24 AF XY: 0.214 AC XY: 14915 AN XY: 69856

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5900112; hg19: chr9-117783551;