rs2856451

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.11531-25T>C 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 0.55 ( 19762 hom., cov: 15)

Exomes 𝑓: 0.55 ( 151469 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.768

Publications

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

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=-0.84).

BP6

Variant 6-32043581-A-G is Benign according to our data. Variant chr6-32043581-A-G is described in ClinVar as Benign. ClinVar VariationId is 261111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 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.11531-25T>C	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12272-25T>C	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.11525-25T>C	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.11531-25T>C	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.818-25T>C	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1358-25T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

70365

AN:

128312

Hom.:

19733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.758

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.578

GnomAD2 exomes

AF:

0.591

AC:

131899

AN:

223084

AF XY:

0.597

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.549

AC:

538049

AN:

979198

Hom.:

151469

Cov.:

AF XY:

0.557

AC XY:

281138

AN XY:

504758

show subpopulations

African (AFR)

AF:

0.472

AC:

11262

AN:

23856

American (AMR)

AF:

0.663

AC:

28953

AN:

43642

Ashkenazi Jewish (ASJ)

AF:

0.757

AC:

17255

AN:

22804

East Asian (EAS)

AF:

0.480

AC:

17702

AN:

36878

South Asian (SAS)

AF:

0.658

AC:

49720

AN:

75594

European-Finnish (FIN)

AF:

0.631

AC:

23926

AN:

37924

Middle Eastern (MID)

AF:

0.671

AC:

2248

AN:

3352

European-Non Finnish (NFE)

AF:

0.524

AC:

361776

AN:

690592

Other (OTH)

AF:

0.566

AC:

25207

AN:

44556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11643

23286

34929

46572

58215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7910

15820

23730

31640

39550

<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:

0.549

AC:

70450

AN:

128428

Hom.:

19762

Cov.:

AF XY:

0.556

AC XY:

34253

AN XY:

61590

show subpopulations

African (AFR)

AF:

0.464

AC:

15298

AN:

32978

American (AMR)

AF:

0.627

AC:

8080

AN:

12890

Ashkenazi Jewish (ASJ)

AF:

0.758

AC:

2310

AN:

3046

East Asian (EAS)

AF:

0.431

AC:

1798

AN:

4172

South Asian (SAS)

AF:

0.637

AC:

2249

AN:

3528

European-Finnish (FIN)

AF:

0.646

AC:

5625

AN:

8714

Middle Eastern (MID)

AF:

0.660

AC:

173

AN:

262

European-Non Finnish (NFE)

AF:

0.552

AC:

33354

AN:

60396

Other (OTH)

AF:

0.583

AC:

956

AN:

1640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1373

2747

4120

5494

6867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.522

Hom.:

2657

Bravo

AF:

0.550

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ehlers-Danlos syndrome due to tenascin-X deficiency (1)

not provided (1)

not specified (1)

Vesicoureteral reflux 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over