rs3789875

Positions:

• chr9-115033009-C-A
• chr9-115033009-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002160.4(TNC):​c.5788-1324G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,156 control chromosomes in the GnomAD database, including 3,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3620 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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]

TNC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4	c.5788-1324G>T		intron_variant		ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5788-1324G>T		intron_variant		1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31030 AN: 152036 Hom.: 3621 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 31029 AN: 152156 Hom.: 3620 Cov.: 32 AF XY: 0.200 AC XY: 14888 AN XY: 74386

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.205

Alfa AF: 0.258 Hom.: 7265

Bravo AF: 0.198

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.74

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: rs3789875; hg19: chr9-117795288;