6-32067917-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.6288G>A(p.Pro2096Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 1,612,468 control chromosomes in the GnomAD database, including 9,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 465 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9493 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.93

Publications

16 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=-0.59).

BP6

Variant 6-32067917-C-T is Benign according to our data. Variant chr6-32067917-C-T is described in ClinVar as Benign. ClinVar VariationId is 261146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.6288G>A	p.Pro2096Pro	synonymous_variant	Exon 18 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.7029G>A	p.Pro2343Pro	synonymous_variant	Exon 19 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.6288G>A	p.Pro2096Pro	synonymous_variant	Exon 18 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.6288G>A	p.Pro2096Pro	synonymous_variant	Exon 18 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.7029G>A	p.Pro2343Pro	synonymous_variant	Exon 19 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.6288G>A	p.Pro2096Pro	synonymous_variant	Exon 18 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0628

AC:

9544

AN:

152040

Hom.:

465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0797

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0474

GnomAD2 exomes

AF:

0.0602

AC:

14790

AN:

245642

AF XY:

0.0592

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.00162

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.102

AC:

148267

AN:

1460310

Hom.:

9493

Cov.:

AF XY:

0.0982

AC XY:

71369

AN XY:

726444

show subpopulations

African (AFR)

AF:

0.0146

AC:

490

AN:

33474

American (AMR)

AF:

0.0230

AC:

1028

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1274

AN:

26136

East Asian (EAS)

AF:

0.000907

AC:

AN:

39700

South Asian (SAS)

AF:

0.000719

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.0811

AC:

4262

AN:

52548

Middle Eastern (MID)

AF:

0.0131

AC:

AN:

5340

European-Non Finnish (NFE)

AF:

0.122

AC:

135768

AN:

1111842

Other (OTH)

AF:

0.0875

AC:

5277

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

9924

19848

29771

39695

49619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4928

9856

14784

19712

24640

<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:

0.0627

AC:

9541

AN:

152158

Hom.:

465

Cov.:

AF XY:

0.0583

AC XY:

4339

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0155

AC:

642

AN:

41510

American (AMR)

AF:

0.0305

AC:

466

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3470

East Asian (EAS)

AF:

0.000967

AC:

AN:

5170

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0797

AC:

845

AN:

10608

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7242

AN:

67972

Other (OTH)

AF:

0.0469

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

438

875

1313

1750

2188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0741

Hom.:

263

Bravo

AF:

0.0575

EpiCase

AF:

0.0957

EpiControl

AF:

0.0874

ClinVar

Significance: 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: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

- -

Cardiovascular phenotype

Benign:1

Dec 24, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.76

(source)

DANN

Benign

0.65

PhyloP100

-5.9

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