NM_002160.4:c.6499G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002160.4(TNC):​c.6499G>C​(p.Val2167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2167I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

TNC
NM_002160.4 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNCNM_002160.4 linkc.6499G>C p.Val2167Leu missense_variant Exon 28 of 28 ENST00000350763.9 NP_002151.2 P24821-1Q4LE33B4E1W8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNCENST00000350763.9 linkc.6499G>C p.Val2167Leu missense_variant Exon 28 of 28 1 NM_002160.4 ENSP00000265131.4 P24821-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
.;T;.;T;.;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;.
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.62
D;D;D;D;D;D
MetaSVM
Uncertain
0.21
D
MutationAssessor
Benign
1.8
.;L;.;.;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.5
.;N;N;N;N;N
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
.;D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D
Polyphen
0.99
.;D;.;D;.;.
Vest4
0.58
MutPred
0.80
.;Loss of MoRF binding (P = 0.1251);.;.;.;.;
MVP
0.85
MPC
0.66
ClinPred
0.97
D
GERP RS
5.1
Varity_R
0.87
gMVP
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149752009; hg19: chr9-117783543; API