rs61737743

chr9-115077997-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002160.4(TNC):c.2620A>G(p.Ile874Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,614,216 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (36 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.873

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072051883).
• BP6: Variant 9-115077997-T-C is Benign according to our data. Variant chr9-115077997-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1557/152330) while in subpopulation AFR AF= 0.0358 (1488/41592). AF 95% confidence interval is 0.0343. There are 32 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1546 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.2620A>G	p.Ile874Val	missense_variant	7/28	ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.2620A>G	p.Ile874Val	missense_variant	7/28	1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-6258T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1546 AN: 152212 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00285 AC: 717 AN: 251428 Hom.: 17 AF XY: 0.00199 AC XY: 271 AN XY: 135890

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00114 AC: 1662 AN: 1461886 Hom.: 36 Cov.: 31 AF XY: 0.000978 AC XY: 711 AN XY: 727246

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.0102 AC: 1557 AN: 152330 Hom.: 32 Cov.: 32 AF XY: 0.00964 AC XY: 718 AN XY: 74482

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00217 Hom.: 8

Bravo AF: 0.0115

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0345 AC: 152

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00348 AC: 422

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 14, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 24, 2017	- -

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	0.093
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.94
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.75	T;T;T;T;T;.
MetaRNN	Benign	0.0072	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.19	N;N;N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.14	T;T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T;T
Polyphen		0.0010, 0.0080	.;B;.;B;.;.
Vest4		0.083
MVP		0.35
MPC		0.13
ClinPred		0.0029	T
GERP RS		4.3
Varity_R		0.074
gMVP		0.22

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: rs61737743; hg19: chr9-117840276;