rs4711283

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.11547A>G(p.Thr3849Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 267 hom., cov: 13)

Exomes 𝑓: 0.067 ( 3017 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.204

Publications

2 publications found

Variant links:

Genes affected

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TNXB Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome due to tenascin-X deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina, PanelApp Australia, Orphanet
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
vesicoureteral reflux 8
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TNXB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-32043540-T-C is Benign according to our data. Variant chr6-32043540-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.204 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TNXB	NM_001365276.2 link	c.11547A>G	p.Thr3849Thr	synonymous_variant	Exon 36 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12288A>G	p.Thr4096Thr	synonymous_variant	Exon 37 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.11541A>G	p.Thr3847Thr	synonymous_variant	Exon 36 of 44		NP_061978.6
TNXB	NM_032470.4 link	c.834A>G	p.Thr278Thr	synonymous_variant	Exon 5 of 13		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.11547A>G	p.Thr3849Thr	synonymous_variant	Exon 36 of 44		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

7266

AN:

121526

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.0155

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.0777

Gnomad NFE

AF:

0.0507

Gnomad OTH

AF:

0.0688

GnomAD2 exomes

AF:

0.0820

AC:

15854

AN:

193266

AF XY:

0.0872

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.0575

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0729

GnomAD4 exome

AF:

0.0675

AC:

55769

AN:

826264

Hom.:

3017

Cov.:

AF XY:

0.0724

AC XY:

31164

AN XY:

430486

show subpopulations

African (AFR)

AF:

0.0704

AC:

1487

AN:

21120

American (AMR)

AF:

0.0591

AC:

2430

AN:

41106

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

1083

AN:

20676

East Asian (EAS)

AF:

0.209

AC:

7572

AN:

36190

South Asian (SAS)

AF:

0.171

AC:

12045

AN:

70400

European-Finnish (FIN)

AF:

0.0597

AC:

2173

AN:

36378

Middle Eastern (MID)

AF:

0.0669

AC:

197

AN:

2944

European-Non Finnish (NFE)

AF:

0.0468

AC:

26096

AN:

557978

Other (OTH)

AF:

0.0680

AC:

2686

AN:

39472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

2405

4811

7216

9622

12027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.0600

AC:

7296

AN:

121638

Hom.:

267

Cov.:

AF XY:

0.0619

AC XY:

3579

AN XY:

57784

show subpopulations

African (AFR)

AF:

0.0677

AC:

2040

AN:

30118

American (AMR)

AF:

0.0558

AC:

669

AN:

11998

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

145

AN:

3104

East Asian (EAS)

AF:

0.131

AC:

530

AN:

4048

South Asian (SAS)

AF:

0.135

AC:

447

AN:

3320

European-Finnish (FIN)

AF:

0.0457

AC:

374

AN:

8188

Middle Eastern (MID)

AF:

0.0803

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0507

AC:

2956

AN:

58350

Other (OTH)

AF:

0.0691

AC:

101

AN:

1462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

308

616

923

1231

1539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0590

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.8

(source)

DANN

Benign

0.70

PhyloP100

-0.20

Mutation Taster

=96/4

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

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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