NM_002160.4:c.6022G>C

Variant names:

• chr9-115030304-C-G
• rs13321
• NM_002160.4:c.6022G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.6022G>C​(p.Glu2008Gln) variant causes a missense change. The variant allele was found at a frequency of 0.707 in 1,613,310 control chromosomes in the GnomAD database, including 404,310 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38313 hom., cov: 32)
  • Exomes 𝑓: 0.71 (365997 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.44
• Publications: 57 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.3580927E-6).
• BP6: Variant 9-115030304-C-G is Benign according to our data. Variant chr9-115030304-C-G is described in ClinVar as Benign. ClinVar VariationId is 1259794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 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.6022G>C	p.Glu2008Gln	missense	Exon 24 of 28	NP_002151.2
	TNC	NM_001439065.1		c.6571G>C	p.Glu2191Gln	missense	Exon 26 of 30	NP_001425994.1
	TNC	NM_001439066.1		c.6571G>C	p.Glu2191Gln	missense	Exon 27 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.6022G>C	p.Glu2008Gln	missense	Exon 24 of 28	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.5203G>C	p.Glu1735Gln	missense	Exon 21 of 25	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.4933G>C	p.Glu1645Gln	missense	Exon 20 of 24	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107631 AN: 151972 Hom.: 38263 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.682 AC: 171202 AN: 250990 AF XY: 0.680

Gnomad AFR exome AF: 0.726

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.723

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.688

GnomAD4 exome AF: 0.707 AC: 1032366 AN: 1461220 Hom.: 365997 Cov.: 50 AF XY: 0.705 AC XY: 512219 AN XY: 726846

African (AFR) AF: 0.739 AC: 24731 AN: 33464

American (AMR) AF: 0.649 AC: 29005 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 16224 AN: 26124

East Asian (EAS) AF: 0.551 AC: 21876 AN: 39692

South Asian (SAS) AF: 0.642 AC: 55336 AN: 86210

European-Finnish (FIN) AF: 0.729 AC: 38918 AN: 53412

Middle Eastern (MID) AF: 0.677 AC: 3898 AN: 5760

European-Non Finnish (NFE) AF: 0.720 AC: 800482 AN: 1111478

Other (OTH) AF: 0.694 AC: 41896 AN: 60360

GnomAD4 genome AF: 0.708 AC: 107731 AN: 152090 Hom.: 38313 Cov.: 32 AF XY: 0.706 AC XY: 52520 AN XY: 74352

African (AFR) AF: 0.735 AC: 30507 AN: 41506

American (AMR) AF: 0.683 AC: 10447 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2850 AN: 5148

South Asian (SAS) AF: 0.634 AC: 3049 AN: 4808

European-Finnish (FIN) AF: 0.718 AC: 7598 AN: 10580

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48702 AN: 67970

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.706 Hom.: 28739

Bravo AF: 0.704

TwinsUK AF: 0.713 AC: 2645

ALSPAC AF: 0.713 AC: 2748

ESP6500AA AF: 0.735 AC: 3238

ESP6500EA AF: 0.705 AC: 6061

ExAC AF: 0.685 AC: 83191

Asia WGS AF: 0.632 AC: 2197 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 56 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.23
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.031
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0000074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		6.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.27
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.083
MPC		0.15
ClinPred		0.012	T
GERP RS		5.3
Varity_R		0.26
gMVP		0.48
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: rs13321; hg19: chr9-117792583; COSMIC: COSV60785451;