rs1757095

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001439065.1(TNC):c.1616A>T(p.Gln539Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. Q539R) has been classified as Benign.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TNC
NM_001439065.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0600

Publications

41 publications found

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]

TNC links:

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]

DELEC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3265983).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439065.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	NM_002160.4	MANE Select	c.1616A>T	p.Gln539Leu	missense	Exon 3 of 28	NP_002151.2
TNC	NM_001439065.1		c.1616A>T	p.Gln539Leu	missense	Exon 3 of 30	NP_001425994.1
TNC	NM_001439066.1		c.1616A>T	p.Gln539Leu	missense	Exon 4 of 31	NP_001425995.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	ENST00000350763.9	TSL:1 MANE Select	c.1616A>T	p.Gln539Leu	missense	Exon 3 of 28	ENSP00000265131.4
TNC	ENST00000423613.6	TSL:1	c.1616A>T	p.Gln539Leu	missense	Exon 3 of 25	ENSP00000411406.2
TNC	ENST00000542877.6	TSL:1	c.1616A>T	p.Gln539Leu	missense	Exon 3 of 24	ENSP00000442242.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251018

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.7

(source)

DANN

Benign

0.92

DEOGEN2

Uncertain

0.64

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.23

M_CAP

Benign

0.0082

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

PhyloP100

0.060

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.074

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.0

Vest4

0.38

MutPred

0.56

Gain of catalytic residue at Q539 (P = 0.0675)

MVP

0.36

MPC

0.19

ClinPred

0.53

GERP RS

0.11

Varity_R

0.26

gMVP

0.71

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over