chr9-115029385-C-T

Variant names:

• chr9-115029385-C-T
• rs79563958
• NM_002160.4:c.6144G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 1P and 17B. PP3 BP6_Very_Strong BP7 BA1

The NM_002160.4(TNC):​c.6144G>A​(p.Gly2048Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,002 control chromosomes in the GnomAD database, including 793 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (120 hom., cov: 32)
  • Exomes 𝑓: 0.011 (673 hom.)
• Consequence: TNC NM_002160.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.549
• Publications: 5 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 -16 ACMG points.

• PP3: REVEL computational evidence supports a deleterious effect, 0.756
• BP6: Variant 9-115029385-C-T is Benign according to our data. Variant chr9-115029385-C-T is described in ClinVar as Benign. ClinVar VariationId is 586836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.549 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0968 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.6144G>A	p.Gly2048Gly	synonymous	Exon 25 of 28	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.6693G>A	p.Gly2231Gly	synonymous	Exon 27 of 30	NP_001425994.1
	TNC	NM_001439066.1		c.6693G>A	p.Gly2231Gly	synonymous	Exon 28 of 31	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.6144G>A	p.Gly2048Gly	synonymous	Exon 25 of 28	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5325G>A	p.Gly1775Gly	synonymous	Exon 22 of 25	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5055G>A	p.Gly1685Gly	synonymous	Exon 21 of 24	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2575 AN: 152044 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.0322 AC: 8097 AN: 251320 AF XY: 0.0294

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.00892

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0111 AC: 16209 AN: 1461840 Hom.: 673 Cov.: 31 AF XY: 0.0117 AC XY: 8493 AN XY: 727228

African (AFR) AF: 0.00218 AC: 73 AN: 33478

American (AMR) AF: 0.119 AC: 5305 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0908 AC: 3604 AN: 39700

South Asian (SAS) AF: 0.0455 AC: 3922 AN: 86256

European-Finnish (FIN) AF: 0.00848 AC: 453 AN: 53418

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.00182 AC: 2028 AN: 1111972

Other (OTH) AF: 0.0134 AC: 811 AN: 60392

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152162 Hom.: 120 Cov.: 32 AF XY: 0.0206 AC XY: 1530 AN XY: 74380

African (AFR) AF: 0.00253 AC: 105 AN: 41500

American (AMR) AF: 0.0900 AC: 1377 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.104 AC: 539 AN: 5178

South Asian (SAS) AF: 0.0525 AC: 252 AN: 4802

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00219 AC: 149 AN: 68006

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.00542 Hom.: 16

Bravo AF: 0.0223

Asia WGS AF: 0.0620 AC: 215 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00184

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 56 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs79563958; hg19: chr9-117791664; COSMIC: COSV60784411; COSMIC: COSV60784411;