rs11755562

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001365276.2(TNXB):c.12378C>T(p.Asp4126Asp) 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0084 ( 16 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.51

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=-0.77).

BP6

Variant 6-32042103-G-A is Benign according to our data. Variant chr6-32042103-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 261123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0084 (4220/502122) while in subpopulation EAS AF = 0.043 (1355/31478). AF 95% confidence interval is 0.0411. There are 16 homozygotes in GnomAdExome4. There are 2317 alleles in the male GnomAdExome4 subpopulation. Median coverage is 5. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TNXB	NM_001365276.2 link	c.12378C>T	p.Asp4126Asp	synonymous_variant	Exon 42 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.13119C>T	p.Asp4373Asp	synonymous_variant	Exon 43 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.12372C>T	p.Asp4124Asp	synonymous_variant	Exon 42 of 44		NP_061978.6
TNXB	NM_032470.4 link	c.1665C>T	p.Asp555Asp	synonymous_variant	Exon 11 of 13		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.12378C>T	p.Asp4126Asp	synonymous_variant	Exon 42 of 44		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

418

AN:

69564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00789

Gnomad ASJ

AF:

0.0362

Gnomad EAS

AF:

0.0122

Gnomad SAS

AF:

0.0113

Gnomad FIN

AF:

0.000265

Gnomad MID

AF:

0.0202

Gnomad NFE

AF:

0.00580

Gnomad OTH

AF:

0.00820

GnomAD2 exomes

AF:

0.00735

AC:

685

AN:

93208

AF XY:

0.00791

show subpopulations

Gnomad AFR exome

AF:

0.000838

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.00840

AC:

4220

AN:

502122

Hom.:

Cov.:

AF XY:

0.00873

AC XY:

2317

AN XY:

265334

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

14768

American (AMR)

AF:

0.00503

AC:

154

AN:

30608

Ashkenazi Jewish (ASJ)

AF:

0.0295

AC:

459

AN:

15536

East Asian (EAS)

AF:

0.0430

AC:

1355

AN:

31478

South Asian (SAS)

AF:

0.0117

AC:

622

AN:

53206

European-Finnish (FIN)

AF:

0.000913

AC:

AN:

30654

Middle Eastern (MID)

AF:

0.0265

AC:

AN:

2192

European-Non Finnish (NFE)

AF:

0.00443

AC:

1310

AN:

295654

Other (OTH)

AF:

0.00731

AC:

205

AN:

28026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

184

367

551

734

918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00599

AC:

417

AN:

69612

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

198

AN XY:

30552

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

17352

American (AMR)

AF:

0.00787

AC:

AN:

6226

Ashkenazi Jewish (ASJ)

AF:

0.0362

AC:

AN:

1740

East Asian (EAS)

AF:

0.0123

AC:

AN:

3012

South Asian (SAS)

AF:

0.0113

AC:

AN:

2040

European-Finnish (FIN)

AF:

0.000265

AC:

AN:

3770

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.00580

AC:

197

AN:

33980

Other (OTH)

AF:

0.00806

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00879

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Jul 08, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

(source)

DANN

Benign

0.90

PhyloP100

-6.5

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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