rs199828189

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001365276.2(TNXB):c.9440-12_9440-10delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,607,978 control chromosomes in the GnomAD database, including 160 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 138 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.249

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 -16 ACMG points.

BP6

Variant 6-32049596-GAGA-G is Benign according to our data. Variant chr6-32049596-GAGA-G is described in ClinVar as Benign. ClinVar VariationId is 261176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00554 (843/152252) while in subpopulation AMR AF = 0.031 (474/15304). AF 95% confidence interval is 0.0287. There are 22 homozygotes in GnomAd4. There are 480 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.9440-12_9440-10delTCT	intron_variant	Intron 27 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.10181-12_10181-10delTCT	intron_variant	Intron 28 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.9434-12_9434-10delTCT	intron_variant	Intron 27 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.9440-12_9440-10delTCT	intron_variant	Intron 27 of 43		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.10181-12_10181-10delTCT	intron_variant	Intron 28 of 44			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.9440-12_9440-10delTCT	intron_variant	Intron 27 of 43	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00550

AC:

837

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.0103

AC:

2483

AN:

241676

AF XY:

0.00785

show subpopulations

Gnomad AFR exome

AF:

0.000422

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00476

AC:

6936

AN:

1455726

Hom.:

138

AF XY:

0.00436

AC XY:

3152

AN XY:

723404

show subpopulations

African (AFR)

AF:

0.000480

AC:

AN:

33300

American (AMR)

AF:

0.0454

AC:

2020

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.0000769

AC:

AN:

26006

East Asian (EAS)

AF:

0.0413

AC:

1634

AN:

39568

South Asian (SAS)

AF:

0.000325

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00761

AC:

396

AN:

52064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

0.00241

AC:

2670

AN:

1108640

Other (OTH)

AF:

0.00283

AC:

170

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

404

809

1213

1618

2022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.00554

AC:

843

AN:

152252

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

480

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41552

American (AMR)

AF:

0.0310

AC:

474

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0209

AC:

108

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00659

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00246

AC:

167

AN:

67994

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

107

143

179

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:

0.00284

Hom.:

Bravo

AF:

0.00685

Asia WGS

AF:

0.00924

AC:

AN:

3478

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

- -

Ehlers-Danlos syndrome

Benign:1

Jul 22, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 14, 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

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: 39

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