rs2239689

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.6842-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,564,790 control chromosomes in the GnomAD database, including 75,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6432 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69187 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.391

Publications

44 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-32062507-G-A is Benign according to our data. Variant chr6-32062507-G-A is described in ClinVar as Benign. ClinVar VariationId is 261152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 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
TNXB	NM_001365276.2	MANE Select	c.6842-24C>T	intron	N/A	NP_001352205.1
TNXB	NM_001428335.1		c.7583-24C>T	intron	N/A	NP_001415264.1
TNXB	NM_019105.8		c.6842-24C>T	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNXB	ENST00000644971.2	MANE Select	c.6842-24C>T	intron	N/A	ENSP00000496448.1
TNXB	ENST00000647633.1		c.7583-24C>T	intron	N/A	ENSP00000497649.1
TNXB	ENST00000375244.7	TSL:5	c.6842-24C>T	intron	N/A	ENSP00000364393.3

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39048

AN:

151926

Hom.:

6425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0601

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.335

AC:

62709

AN:

187348

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.0550

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.305

AC:

431406

AN:

1412746

Hom.:

69187

Cov.:

AF XY:

0.306

AC XY:

213101

AN XY:

696814

show subpopulations

African (AFR)

AF:

0.0538

AC:

1757

AN:

32628

American (AMR)

AF:

0.441

AC:

16757

AN:

38038

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

11234

AN:

24800

East Asian (EAS)

AF:

0.251

AC:

9616

AN:

38262

South Asian (SAS)

AF:

0.253

AC:

20421

AN:

80680

European-Finnish (FIN)

AF:

0.387

AC:

19077

AN:

49308

Middle Eastern (MID)

AF:

0.335

AC:

1886

AN:

5638

European-Non Finnish (NFE)

AF:

0.307

AC:

333545

AN:

1084792

Other (OTH)

AF:

0.292

AC:

17113

AN:

58600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16521

33042

49563

66084

82605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10784

21568

32352

43136

53920

<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:

0.257

AC:

39061

AN:

152044

Hom.:

6432

Cov.:

AF XY:

0.263

AC XY:

19527

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0600

AC:

2490

AN:

41526

American (AMR)

AF:

0.377

AC:

5761

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

1610

AN:

3466

East Asian (EAS)

AF:

0.205

AC:

1061

AN:

5172

South Asian (SAS)

AF:

0.245

AC:

1179

AN:

4818

European-Finnish (FIN)

AF:

0.400

AC:

4218

AN:

10534

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.320

AC:

21719

AN:

67944

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1363

2725

4088

5450

6813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.309

Hom.:

26257

Bravo

AF:

0.249

Asia WGS

AF:

0.227

AC:

790

AN:

3478

ClinVar

ClinVar submissions as Germline

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

-0.90

CADD

Benign

3.3

(source)

DANN

Benign

0.58

PhyloP100

0.39

PromoterAI

0.019

Neutral

(source)

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over