6-32044556-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001365276.2(TNXB):c.11088T>A(p.Thr3696Thr) variant causes a synonymous 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 0.18 ( 33 hom., cov: 3)

Exomes 𝑓: 0.24 ( 1170 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.63

Publications

2 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 6-32044556-A-T is Benign according to our data. Variant chr6-32044556-A-T is described in ClinVar as Benign. ClinVar VariationId is 261101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

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	HGVSp	Effect	Exon Rank	Protein
TNXB	NM_001365276.2	MANE Select	c.11088T>A	p.Thr3696Thr	synonymous	Exon 33 of 44	NP_001352205.1
TNXB	NM_001428335.1		c.11829T>A	p.Thr3943Thr	synonymous	Exon 34 of 45	NP_001415264.1
TNXB	NM_019105.8		c.11082T>A	p.Thr3694Thr	synonymous	Exon 33 of 44	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNXB	ENST00000644971.2	MANE Select	c.11088T>A	p.Thr3696Thr	synonymous	Exon 33 of 44	ENSP00000496448.1
TNXB	ENST00000451343.4	TSL:1	c.375T>A	p.Thr125Thr	synonymous	Exon 2 of 13	ENSP00000407685.1
TNXB	ENST00000490077.5	TSL:1	n.915T>A		non_coding_transcript_exon	Exon 3 of 14

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

1478

AN:

8170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.140

GnomAD2 exomes

AF:

0.223

AC:

11360

AN:

50910

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.245

AC:

95028

AN:

388208

Hom.:

1170

Cov.:

AF XY:

0.244

AC XY:

49790

AN XY:

203822

show subpopulations

African (AFR)

AF:

0.0519

AC:

588

AN:

11340

American (AMR)

AF:

0.300

AC:

4740

AN:

15774

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

3874

AN:

11632

East Asian (EAS)

AF:

0.218

AC:

5780

AN:

26554

South Asian (SAS)

AF:

0.208

AC:

8634

AN:

41570

European-Finnish (FIN)

AF:

0.287

AC:

6784

AN:

23630

Middle Eastern (MID)

AF:

0.260

AC:

426

AN:

1638

European-Non Finnish (NFE)

AF:

0.252

AC:

58724

AN:

233378

Other (OTH)

AF:

0.241

AC:

5478

AN:

22692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2697

5394

8090

10787

13484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.180

AC:

1472

AN:

8168

Hom.:

Cov.:

AF XY:

0.177

AC XY:

603

AN XY:

3410

show subpopulations

African (AFR)

AF:

0.0407

AC:

AN:

1966

American (AMR)

AF:

0.232

AC:

231

AN:

994

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

AN:

272

East Asian (EAS)

AF:

0.174

AC:

122

AN:

700

South Asian (SAS)

AF:

0.226

AC:

101

AN:

446

European-Finnish (FIN)

AF:

0.321

AC:

AN:

112

Middle Eastern (MID)

AF:

0.196

AC:

AN:

European-Non Finnish (NFE)

AF:

0.228

AC:

792

AN:

3474

Other (OTH)

AF:

0.147

AC:

AN:

136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.0415

Hom.:

ClinVar

ClinVar submissions as Germline

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

-1.0

CADD

Benign

0.58

(source)

DANN

Benign

0.85

PhyloP100

-4.6

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