6-32062138-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365276.2(TNXB):c.7168+19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,604,262 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 99 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.181

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-32062138-G-T is Benign according to our data. Variant chr6-32062138-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00484 (737/152310) while in subpopulation SAS AF = 0.0135 (65/4830). AF 95% confidence interval is 0.0108. There are 4 homozygotes in GnomAd4. There are 397 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.7168+19C>A	intron_variant	Intron 20 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.7909+19C>A	intron_variant	Intron 21 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.7168+19C>A	intron_variant	Intron 20 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.7168+19C>A	intron_variant	Intron 20 of 43		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.7909+19C>A	intron_variant	Intron 21 of 44			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.7168+19C>A	intron_variant	Intron 20 of 43	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00485

AC:

738

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0134

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00646

AC:

1545

AN:

239338

AF XY:

0.00717

show subpopulations

Gnomad AFR exome

AF:

0.000718

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.000521

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00525

AC:

7619

AN:

1451952

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

4068

AN XY:

720708

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

33262

American (AMR)

AF:

0.00473

AC:

209

AN:

44226

Ashkenazi Jewish (ASJ)

AF:

0.0296

AC:

764

AN:

25808

East Asian (EAS)

AF:

0.0398

AC:

1569

AN:

39460

South Asian (SAS)

AF:

0.0119

AC:

1017

AN:

85406

European-Finnish (FIN)

AF:

0.000690

AC:

AN:

52178

Middle Eastern (MID)

AF:

0.0228

AC:

131

AN:

5734

European-Non Finnish (NFE)

AF:

0.00310

AC:

3432

AN:

1105878

Other (OTH)

AF:

0.00653

AC:

392

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

446

893

1339

1786

2232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<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:

0.00484

AC:

737

AN:

152310

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

397

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41574

American (AMR)

AF:

0.00654

AC:

100

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3468

East Asian (EAS)

AF:

0.0133

AC:

AN:

5182

South Asian (SAS)

AF:

0.0135

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00484

AC:

329

AN:

68016

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

123

164

205

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:

0.00946

Hom.:

Bravo

AF:

0.00521

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 09, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.84

CADD

Benign

8.6

(source)

DANN

Benign

0.74

PhyloP100

-0.18

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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