Genetic Variant TNC:p.Thr1734Thr (chr9-115042265-T-C) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002160.4(TNC):c.5202A>G(p.Thr1734Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,764 control chromosomes in the GnomAD database, including 56,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8182 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48807 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.120

Publications

31 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.018).

BP6

Variant 9-115042265-T-C is Benign according to our data. Variant chr9-115042265-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.5202A>G	p.Thr1734Thr	synonymous_variant	Exon 18 of 28	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9 link	c.5202A>G	p.Thr1734Thr	synonymous_variant	Exon 18 of 28	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46907

AN:

152016

Hom.:

8172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.242

AC:

60843

AN:

251276

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.251

AC:

367515

AN:

1461630

Hom.:

48807

Cov.:

AF XY:

0.246

AC XY:

178947

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.483

AC:

16162

AN:

33474

American (AMR)

AF:

0.247

AC:

11050

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5210

AN:

26132

East Asian (EAS)

AF:

0.115

AC:

4548

AN:

39694

South Asian (SAS)

AF:

0.113

AC:

9728

AN:

86234

European-Finnish (FIN)

AF:

0.296

AC:

15794

AN:

53404

Middle Eastern (MID)

AF:

0.200

AC:

1153

AN:

5766

European-Non Finnish (NFE)

AF:

0.260

AC:

288939

AN:

1111836

Other (OTH)

AF:

0.247

AC:

14931

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

14752

29504

44257

59009

73761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9788

19576

29364

39152

48940

<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

AF:

0.309

AC:

46963

AN:

152134

Hom.:

8182

Cov.:

AF XY:

0.303

AC XY:

22513

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.478

AC:

19847

AN:

41478

American (AMR)

AF:

0.247

AC:

3777

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

684

AN:

3470

East Asian (EAS)

AF:

0.138

AC:

717

AN:

5180

South Asian (SAS)

AF:

0.117

AC:

565

AN:

4816

European-Finnish (FIN)

AF:

0.280

AC:

2967

AN:

10598

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17533

AN:

67992

Other (OTH)

AF:

0.268

AC:

563

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1593

3186

4779

6372

7965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.266

Hom.:

9188

Bravo

AF:

0.315

Asia WGS

AF:

0.137

AC:

479

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.249

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.76

(source)

DANN

Benign

0.36

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over