rs2734313

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365276.2(TNXB):c.11650+10C>G variant causes a intron 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 Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 4178 hom., cov: 7)

Exomes 𝑓: 0.45 ( 50170 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.13

Publications

4 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: Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
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

new If you want to explore the variant's impact on the transcript NM_001365276.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-32043427-G-C is Benign according to our data. Variant chr6-32043427-G-C is described in ClinVar as Benign. ClinVar VariationId is 261115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	NM_001365276.2	MANE Select	c.11650+10C>G	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12391+10C>G	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.11644+10C>G	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.11650+10C>G	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.937+10C>G	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1477+10C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

17749

AN:

41826

Hom.:

4176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.464

AC:

35360

AN:

76204

AF XY:

0.450

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.453

AC:

216796

AN:

478920

Hom.:

50170

Cov.:

AF XY:

0.450

AC XY:

113597

AN XY:

252172

show subpopulations

African (AFR)

AF:

0.466

AC:

6497

AN:

13956

American (AMR)

AF:

0.575

AC:

15842

AN:

27568

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

8624

AN:

15104

East Asian (EAS)

AF:

0.445

AC:

13725

AN:

30858

South Asian (SAS)

AF:

0.402

AC:

20164

AN:

50146

European-Finnish (FIN)

AF:

0.445

AC:

13058

AN:

29336

Middle Eastern (MID)

AF:

0.496

AC:

1016

AN:

2050

European-Non Finnish (NFE)

AF:

0.444

AC:

125685

AN:

282776

Other (OTH)

AF:

0.449

AC:

12185

AN:

27126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

5132

10263

15395

20526

25658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.424

AC:

17758

AN:

41862

Hom.:

4178

Cov.:

AF XY:

0.425

AC XY:

7617

AN XY:

17932

show subpopulations

African (AFR)

AF:

0.430

AC:

3983

AN:

9272

American (AMR)

AF:

0.489

AC:

2003

AN:

4100

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

637

AN:

1182

East Asian (EAS)

AF:

0.382

AC:

758

AN:

1984

South Asian (SAS)

AF:

0.396

AC:

566

AN:

1428

European-Finnish (FIN)

AF:

0.434

AC:

1114

AN:

2568

Middle Eastern (MID)

AF:

0.414

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.405

AC:

8259

AN:

20394

Other (OTH)

AF:

0.445

AC:

242

AN:

544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

444

888

1333

1777

2221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.445

Hom.:

1916

Bravo

AF:

0.466

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over