6-32043592-G-T

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.11531-36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,197,180 control chromosomes in the GnomAD database, including 8,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1478 hom., cov: 22)

Exomes 𝑓: 0.10 ( 7412 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.899

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 6-32043592-G-T is Benign according to our data. Variant chr6-32043592-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TNXB	NM_001365276.2 link	c.11531-36C>A	intron_variant	Intron 35 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12272-36C>A	intron_variant	Intron 36 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.11525-36C>A	intron_variant	Intron 35 of 43		NP_061978.6
TNXB	NM_032470.4 link	c.818-36C>A	intron_variant	Intron 4 of 12		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.11531-36C>A		intron_variant	Intron 35 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

18460

AN:

141230

Hom.:

1476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.0169

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.133

AC:

30655

AN:

229832

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0670

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.103

AC:

108525

AN:

1055838

Hom.:

7412

Cov.:

AF XY:

0.109

AC XY:

58802

AN XY:

541420

show subpopulations

African (AFR)

AF:

0.210

AC:

5281

AN:

25154

American (AMR)

AF:

0.117

AC:

5163

AN:

44142

Ashkenazi Jewish (ASJ)

AF:

0.0995

AC:

2345

AN:

23558

East Asian (EAS)

AF:

0.182

AC:

6866

AN:

37756

South Asian (SAS)

AF:

0.244

AC:

18931

AN:

77644

European-Finnish (FIN)

AF:

0.0707

AC:

2760

AN:

39064

Middle Eastern (MID)

AF:

0.168

AC:

619

AN:

3694

European-Non Finnish (NFE)

AF:

0.0806

AC:

61031

AN:

757546

Other (OTH)

AF:

0.117

AC:

5529

AN:

47280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4277

8553

12830

17106

21383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1766

3532

5298

7064

8830

<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:

0.131

AC:

18486

AN:

141342

Hom.:

1478

Cov.:

AF XY:

0.132

AC XY:

8988

AN XY:

68348

show subpopulations

African (AFR)

AF:

0.207

AC:

7624

AN:

36846

American (AMR)

AF:

0.142

AC:

2022

AN:

14254

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

355

AN:

3388

East Asian (EAS)

AF:

0.144

AC:

665

AN:

4614

South Asian (SAS)

AF:

0.200

AC:

824

AN:

4110

European-Finnish (FIN)

AF:

0.0594

AC:

586

AN:

9860

Middle Eastern (MID)

AF:

0.208

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0925

AC:

6033

AN:

65214

Other (OTH)

AF:

0.160

AC:

302

AN:

1882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

690

1380

2070

2760

3450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0681

Hom.:

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

-0.94

CADD

Benign

1.4

(source)

DANN

Benign

0.64

PhyloP100

-0.90

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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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