rs9469080

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.6544+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,611,500 control chromosomes in the GnomAD database, including 15,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2200 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12846 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.01

Publications

10 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=-0.97).

BP6

Variant 6-32067650-T-C is Benign according to our data. Variant chr6-32067650-T-C is described in ClinVar as Benign. ClinVar VariationId is 261148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 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.6544+11A>G	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.7285+11A>G	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.6544+11A>G	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.6544+11A>G	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1		c.7285+11A>G	intron	N/A	ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7	TSL:5	c.6544+11A>G	intron	N/A	ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22593

AN:

152070

Hom.:

2189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0618

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.0961

Gnomad OTH

AF:

0.184

GnomAD2 exomes

AF:

0.139

AC:

34197

AN:

245536

AF XY:

0.151

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0954

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0657

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.111

AC:

162260

AN:

1459312

Hom.:

12846

Cov.:

AF XY:

0.119

AC XY:

86210

AN XY:

725614

show subpopulations

African (AFR)

AF:

0.257

AC:

8574

AN:

33390

American (AMR)

AF:

0.102

AC:

4545

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2831

AN:

26008

East Asian (EAS)

AF:

0.109

AC:

4329

AN:

39626

South Asian (SAS)

AF:

0.343

AC:

29535

AN:

86140

European-Finnish (FIN)

AF:

0.0686

AC:

3644

AN:

53118

Middle Eastern (MID)

AF:

0.269

AC:

1539

AN:

5724

European-Non Finnish (NFE)

AF:

0.0898

AC:

99767

AN:

1110526

Other (OTH)

AF:

0.124

AC:

7496

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8284

16568

24851

33135

41419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3796

7592

11388

15184

18980

<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:

0.149

AC:

22627

AN:

152188

Hom.:

2200

Cov.:

AF XY:

0.152

AC XY:

11293

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.250

AC:

10359

AN:

41506

American (AMR)

AF:

0.147

AC:

2250

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

384

AN:

3470

East Asian (EAS)

AF:

0.106

AC:

549

AN:

5184

South Asian (SAS)

AF:

0.297

AC:

1429

AN:

4818

European-Finnish (FIN)

AF:

0.0618

AC:

656

AN:

10612

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0961

AC:

6534

AN:

67994

Other (OTH)

AF:

0.182

AC:

383

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

949

1898

2847

3796

4745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.122

Hom.:

465

Bravo

AF:

0.155

Asia WGS

AF:

0.247

AC:

859

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.1

(source)

DANN

Benign

0.43

PhyloP100

-3.0

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