6-32044502-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.11142G>A(p.Thr3714Thr) 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 0.046 ( 38 hom., cov: 4)

Exomes 𝑓: 0.050 ( 484 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -10.3

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-32044502-C-T is Benign according to our data. Variant chr6-32044502-C-T is described in ClinVar as Benign. ClinVar VariationId is 261102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-10.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.11142G>A	p.Thr3714Thr	synonymous_variant	Exon 33 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.11883G>A	p.Thr3961Thr	synonymous_variant	Exon 34 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.11136G>A	p.Thr3712Thr	synonymous_variant	Exon 33 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 link	c.429G>A	p.Thr143Thr	synonymous_variant	Exon 2 of 13		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.11142G>A	p.Thr3714Thr	synonymous_variant	Exon 33 of 44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

716

AN:

15778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.0814

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.0239

Gnomad FIN

AF:

0.00234

Gnomad MID

AF:

0.0682

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0612

AC:

2929

AN:

47852

AF XY:

0.0608

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0519

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.0607

Gnomad FIN exome

AF:

0.00765

Gnomad NFE exome

AF:

0.0646

Gnomad OTH exome

AF:

0.0711

GnomAD4 exome

AF:

0.0498

AC:

18574

AN:

372862

Hom.:

484

Cov.:

AF XY:

0.0479

AC XY:

9408

AN XY:

196380

show subpopulations

African (AFR)

AF:

0.106

AC:

1081

AN:

10172

American (AMR)

AF:

0.0542

AC:

856

AN:

15794

Ashkenazi Jewish (ASJ)

AF:

0.0535

AC:

630

AN:

11786

East Asian (EAS)

AF:

0.0564

AC:

1275

AN:

22598

South Asian (SAS)

AF:

0.0250

AC:

1032

AN:

41228

European-Finnish (FIN)

AF:

0.0153

AC:

357

AN:

23326

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0539

AC:

12127

AN:

224922

Other (OTH)

AF:

0.0524

AC:

1122

AN:

21410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

582

1165

1747

2330

2912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.0456

AC:

720

AN:

15782

Hom.:

Cov.:

AF XY:

0.0450

AC XY:

289

AN XY:

6418

show subpopulations

African (AFR)

AF:

0.0807

AC:

256

AN:

3172

American (AMR)

AF:

0.0582

AC:

AN:

1512

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

AN:

578

East Asian (EAS)

AF:

0.0322

AC:

AN:

746

South Asian (SAS)

AF:

0.0241

AC:

AN:

456

European-Finnish (FIN)

AF:

0.00234

AC:

AN:

854

Middle Eastern (MID)

AF:

0.0750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0371

AC:

300

AN:

8080

Other (OTH)

AF:

0.0321

AC:

AN:

218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

117

146

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:

0.0542

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 24, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: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

-0.87

CADD

Benign

0.027

(source)

DANN

Benign

0.94

PhyloP100

-10

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over