9-115021272-TAAAA-TAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002160.4(TNC):​c.6496-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 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, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -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 VariationId 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.

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

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

GnomAD2 exomes AF: 0.312 AC: 50561 AN: 161918 AF XY: 0.314

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.334

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

African (AFR) AF: 0.172 AC: 3716 AN: 21662

American (AMR) AF: 0.281 AC: 8231 AN: 29294

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 4371 AN: 17144

East Asian (EAS) AF: 0.241 AC: 6374 AN: 26464

South Asian (SAS) AF: 0.250 AC: 13982 AN: 56028

European-Finnish (FIN) AF: 0.360 AC: 14418 AN: 40030

Middle Eastern (MID) AF: 0.249 AC: 997 AN: 3996

European-Non Finnish (NFE) AF: 0.329 AC: 278570 AN: 847580

Other (OTH) AF: 0.306 AC: 13353 AN: 43674

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

African (AFR) AF: 0.0945 AC: 3661 AN: 38754

American (AMR) AF: 0.204 AC: 2952 AN: 14476

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 517 AN: 3360

East Asian (EAS) AF: 0.152 AC: 755 AN: 4960

South Asian (SAS) AF: 0.141 AC: 633 AN: 4492

European-Finnish (FIN) AF: 0.344 AC: 3153 AN: 9162

Middle Eastern (MID) AF: 0.231 AC: 66 AN: 286

European-Non Finnish (NFE) AF: 0.281 AC: 18505 AN: 65798

Other (OTH) AF: 0.217 AC: 425 AN: 1960

Alfa AF: 0.162 Hom.: 178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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

Other links and lift over

dbSNP: rs5900112; hg19: chr9-117783551;