chr9-115046506-T-A

Position:

• chr9-115046506-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.5029A>T​(p.Ile1677Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,613,834 control chromosomes in the GnomAD database, including 153,510 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (17242 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136268 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.850

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5833974E-4).
• BP6: Variant 9-115046506-T-A is Benign according to our data. Variant chr9-115046506-T-A is described in ClinVar as [Benign]. Clinvar id is 1238979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4	c.5029A>T	p.Ile1677Leu	missense_variant	17/28	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5029A>T	p.Ile1677Leu	missense_variant	17/28	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71588 AN: 151890 Hom.: 17222 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.467

GnomAD3 exomes AF: 0.437 AC: 109906 AN: 251412 Hom.: 24219 AF XY: 0.433 AC XY: 58775 AN XY: 135880

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.433

Gnomad SAS exome AF: 0.401

Gnomad FIN exome AF: 0.472

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.430 AC: 628402 AN: 1461826 Hom.: 136268 Cov.: 58 AF XY: 0.429 AC XY: 312093 AN XY: 727214

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.471 AC: 71644 AN: 152008 Hom.: 17242 Cov.: 32 AF XY: 0.472 AC XY: 35076 AN XY: 74304

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.466

Alfa AF: 0.436 Hom.: 11283

Bravo AF: 0.474

TwinsUK AF: 0.407 AC: 1510

ALSPAC AF: 0.420 AC: 1619

ESP6500AA AF: 0.563 AC: 2482

ESP6500EA AF: 0.431 AC: 3705

ExAC AF: 0.438 AC: 53222

Asia WGS AF: 0.431 AC: 1504 AN: 3478

EpiCase AF: 0.436

EpiControl AF: 0.438

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	This variant is associated with the following publications: (PMID: 16115819) -

Autosomal dominant nonsyndromic hearing loss 56 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.60	T;T;T;.
MetaRNN	Benign	0.00016	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	.;L;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.42	.;T;T;T
Sift4G	Benign	0.76	T;T;T;T
Polyphen		0.0040	.;B;.;.
Vest4		0.26
MutPred		0.44		.;Gain of disorder (P = 0.0919);.;.;
MPC		0.22
ClinPred		0.0071	T
GERP RS		3.4
Varity_R		0.19
gMVP		0.69

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: rs2104772; hg19: chr9-117808785; COSMIC: COSV60782293; COSMIC: COSV60782293;