rs1150757

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.7461C>T(p.Arg2487Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 1,612,690 control chromosomes in the GnomAD database, including 9,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 479 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9485 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.89

Publications

37 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=-0.78).

BP6

Variant 6-32061428-G-A is Benign according to our data. Variant chr6-32061428-G-A is described in ClinVar as [Benign]. Clinvar id is 261160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.89 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.7461C>T	p.Arg2487Arg	synonymous_variant	Exon 21 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.8202C>T	p.Arg2734Arg	synonymous_variant	Exon 22 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.7461C>T	p.Arg2487Arg	synonymous_variant	Exon 21 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.7461C>T	p.Arg2487Arg	synonymous_variant	Exon 21 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.8202C>T	p.Arg2734Arg	synonymous_variant	Exon 22 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.7461C>T	p.Arg2487Arg	synonymous_variant	Exon 21 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9464

AN:

151754

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0703

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0799

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0587

AC:

14408

AN:

245576

AF XY:

0.0578

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0361

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0596

GnomAD4 exome

AF:

0.101

AC:

147413

AN:

1460818

Hom.:

9485

Cov.:

AF XY:

0.0976

AC XY:

70901

AN XY:

726626

show subpopulations

African (AFR)

AF:

0.0143

AC:

478

AN:

33406

American (AMR)

AF:

0.0223

AC:

998

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0399

AC:

1042

AN:

26110

East Asian (EAS)

AF:

0.000176

AC:

AN:

39684

South Asian (SAS)

AF:

0.000220

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0807

AC:

4285

AN:

53080

Middle Eastern (MID)

AF:

0.00573

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.122

AC:

135335

AN:

1111498

Other (OTH)

AF:

0.0864

AC:

5216

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

8410

16820

25229

33639

42049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0623

AC:

9461

AN:

151872

Hom.:

479

Cov.:

AF XY:

0.0579

AC XY:

4302

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0155

AC:

637

AN:

41182

American (AMR)

AF:

0.0296

AC:

452

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0386

AC:

134

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0799

AC:

848

AN:

10612

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7221

AN:

67994

Other (OTH)

AF:

0.0464

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

428

856

1285

1713

2141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0727

Hom.:

265

Bravo

AF:

0.0570

EpiCase

AF:

0.0947

EpiControl

AF:

0.0863

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

-0.78

CADD

Benign

0.65

(source)

DANN

Benign

0.84

PhyloP100

-2.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1150757

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