NM_002160.4:c.6235C>T

Variant names:

• chr9-115026630-G-A
• rs866729657
• NM_002160.4:c.6235C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002160.4(TNC):​c.6235C>T​(p.His2079Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TNC NM_002160.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29308692).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.6235C>T	p.His2079Tyr	missense_variant	Exon 26 of 28	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.6235C>T	p.His2079Tyr	missense_variant	Exon 26 of 28	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461792 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;.;T;.;.
Eigen	Benign	0.012
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	.;N;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.3	D;N;N;N;N;N
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D;D;T;T;T;D
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.85, 0.94	.;P;.;P;.;.
Vest4		0.29
MutPred		0.58		.;Loss of catalytic residue at R2077 (P = 0.0595);.;.;.;.;
MVP		0.73
MPC		0.46
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.48
gMVP		0.48

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: rs866729657; hg19: chr9-117788909;