rs11969759

Variant names:

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.8791+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,598,890 control chromosomes in the GnomAD database, including 4,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 920 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3638 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.81

Publications

16 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=-0.92).

BP6

Variant 6-32053353-C-T is Benign according to our data. Variant chr6-32053353-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.8791+35G>A	intron_variant	Intron 25 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.9532+35G>A	intron_variant	Intron 26 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.8785+35G>A	intron_variant	Intron 25 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.8791+35G>A	intron_variant	Intron 25 of 43		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.9532+35G>A	intron_variant	Intron 26 of 44			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.8791+35G>A	intron_variant	Intron 25 of 43	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14885

AN:

152090

Hom.:

918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.0829

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0855

GnomAD2 exomes

AF:

0.0783

AC:

17934

AN:

229070

AF XY:

0.0731

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.00991

Gnomad EAS exome

AF:

0.0886

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.0626

Gnomad OTH exome

AF:

0.0641

GnomAD4 exome

AF:

0.0642

AC:

92927

AN:

1446682

Hom.:

3638

Cov.:

AF XY:

0.0627

AC XY:

44998

AN XY:

717732

show subpopulations

African (AFR)

AF:

0.164

AC:

5429

AN:

33172

American (AMR)

AF:

0.0844

AC:

3642

AN:

43142

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

280

AN:

25864

East Asian (EAS)

AF:

0.0720

AC:

2828

AN:

39294

South Asian (SAS)

AF:

0.0337

AC:

2865

AN:

84968

European-Finnish (FIN)

AF:

0.159

AC:

8254

AN:

51750

Middle Eastern (MID)

AF:

0.0461

AC:

214

AN:

4638

European-Non Finnish (NFE)

AF:

0.0597

AC:

65902

AN:

1104088

Other (OTH)

AF:

0.0588

AC:

3513

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5498

10996

16495

21993

27491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0978

AC:

14892

AN:

152208

Hom.:

920

Cov.:

AF XY:

0.100

AC XY:

7445

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.162

AC:

6705

AN:

41494

American (AMR)

AF:

0.0720

AC:

1102

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3466

East Asian (EAS)

AF:

0.0825

AC:

427

AN:

5176

South Asian (SAS)

AF:

0.0394

AC:

190

AN:

4828

European-Finnish (FIN)

AF:

0.175

AC:

1856

AN:

10604

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0632

AC:

4295

AN:

68010

Other (OTH)

AF:

0.0851

AC:

180

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

654

1307

1961

2614

3268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0699

Hom.:

528

Bravo

AF:

0.0948

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.046

(source)

DANN

Benign

0.48

PhyloP100

-2.8

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

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rs11969759

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over