9-115029233-G-C

Position:

• chr9-115029233-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002160.4(TNC):​c.6169+127C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 752,576 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0062 (32 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.824

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-115029233-G-C is Benign according to our data. Variant chr9-115029233-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1317855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 823 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.6169+127C>G		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.6169+127C>G		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-55022G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 822 AN: 152086 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00833

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00691

Gnomad OTH AF: 0.00720

GnomAD4 exome AF: 0.00617 AC: 3706 AN: 600372 Hom.: 32 AF XY: 0.00617 AC XY: 1958 AN XY: 317174

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00633

Gnomad4 ASJ exome AF: 0.0000614

Gnomad4 EAS exome AF: 0.0000296

Gnomad4 SAS exome AF: 0.00394

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00654

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.00541 AC: 823 AN: 152204 Hom.: 5 Cov.: 31 AF XY: 0.00584 AC XY: 435 AN XY: 74426

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00831

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00693

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.00464

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.5
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs142249284; hg19: chr9-117791512;