rs397948

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.11387-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 148,600 control chromosomes in the GnomAD database, including 17,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17379 hom., cov: 25)

Exomes 𝑓: 0.39 ( 118367 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: -0.719

Publications

6 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=-0.91).

BP6

Variant 6-32043937-A-G is Benign according to our data. Variant chr6-32043937-A-G is described in ClinVar as Benign. ClinVar VariationId is 261106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 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.11387-45T>C	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12128-45T>C	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.11381-45T>C	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.11387-45T>C	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.674-45T>C	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1214-45T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

69081

AN:

148482

Hom.:

17351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.470

GnomAD2 exomes

AF:

0.413

AC:

100760

AN:

244178

AF XY:

0.420

show subpopulations

Gnomad AFR exome

AF:

0.679

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.527

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.393

AC:

560814

AN:

1426856

Hom.:

118367

Cov.:

AF XY:

0.397

AC XY:

281530

AN XY:

709980

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.688

AC:

22589

AN:

32844

American (AMR)

AF:

0.347

AC:

15436

AN:

44422

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7061

AN:

25822

East Asian (EAS)

AF:

0.438

AC:

17259

AN:

39428

South Asian (SAS)

AF:

0.575

AC:

48855

AN:

85010

European-Finnish (FIN)

AF:

0.375

AC:

19202

AN:

51210

Middle Eastern (MID)

AF:

0.442

AC:

2502

AN:

5666

European-Non Finnish (NFE)

AF:

0.373

AC:

403661

AN:

1083238

Other (OTH)

AF:

0.410

AC:

24249

AN:

59216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

14810

29620

44431

59241

74051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12838

25676

38514

51352

64190

<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:

0.465

AC:

69157

AN:

148600

Hom.:

17379

Cov.:

AF XY:

0.467

AC XY:

33855

AN XY:

72502

show subpopulations

African (AFR)

AF:

0.677

AC:

27278

AN:

40272

American (AMR)

AF:

0.385

AC:

5780

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

914

AN:

3438

East Asian (EAS)

AF:

0.516

AC:

2557

AN:

4958

South Asian (SAS)

AF:

0.562

AC:

2590

AN:

4612

European-Finnish (FIN)

AF:

0.389

AC:

4001

AN:

10274

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.368

AC:

24568

AN:

66766

Other (OTH)

AF:

0.471

AC:

975

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

1556

3111

4667

6222

7778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.378

Hom.:

1948

Bravo

AF:

0.474

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

-0.91

CADD

Benign

0.096

(source)

DANN

Benign

0.20

PhyloP100

-0.72

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over