9-115021264-C-T

Position:

• chr9-115021264-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002160.4(TNC):​c.6499G>A​(p.Val2167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,594,378 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (5 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.64

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010558158).
• BP6: Variant 9-115021264-C-T is Benign according to our data. Variant chr9-115021264-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 805677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115021264-C-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.6499G>A	p.Val2167Ile	missense_variant	28/28	ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.6499G>A	p.Val2167Ile	missense_variant	28/28	1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.78+51603C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 392 AN: 142708 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000979

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000473

Gnomad OTH AF: 0.00104

GnomAD3 exomes AF: 0.000837 AC: 196 AN: 234256 Hom.: 0 AF XY: 0.000684 AC XY: 87 AN XY: 127258

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000238

Gnomad SAS exome AF: 0.0000713

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000743

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000320 AC: 464 AN: 1451556 Hom.: 5 Cov.: 30 AF XY: 0.000304 AC XY: 220 AN XY: 722498

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.000530

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000289

Gnomad4 OTH exome AF: 0.000802

GnomAD4 genome AF: 0.00273 AC: 390 AN: 142822 Hom.: 1 Cov.: 32 AF XY: 0.00274 AC XY: 190 AN XY: 69438

Gnomad4 AFR AF: 0.00928

Gnomad4 AMR AF: 0.000977

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000111

Gnomad4 NFE AF: 0.0000473

Gnomad4 OTH AF: 0.00103

Alfa AF: 0.000478 Hom.: 0

Bravo AF: 0.00317

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000890 AC: 108

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 18, 2019	- -

Autosomal dominant nonsyndromic hearing loss 56 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.97
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;.
MetaRNN	Benign	0.011	T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	0.93	D;D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.63	T
REVEL	Benign	0.24
Sift4G	Benign	0.39	T;T;T;T;T;T
Polyphen		0.98	.;D;.;D;.;.
Vest4		0.18
MVP		0.81
MPC		0.60
ClinPred		0.031	T
GERP RS		5.1
Varity_R		0.57
gMVP		0.19

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: rs149752009; hg19: chr9-117783543;