rs204887

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.7440T>C(p.Tyr2480=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,612,076 control chromosomes in the GnomAD database, including 379,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31805 hom., cov: 31)

Exomes 𝑓: 0.69 ( 347364 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.50

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 6-32061449-A-G is Benign according to our data. Variant chr6-32061449-A-G is described in ClinVar as [Benign]. Clinvar id is 261159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32061449-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.7440T>C	p.Tyr2480=	synonymous_variant	21/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.7440T>C	p.Tyr2480=	synonymous_variant	21/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.7440T>C	p.Tyr2480=	synonymous_variant	21/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.8181T>C	p.Tyr2727=	synonymous_variant	22/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.7440T>C	p.Tyr2480=	synonymous_variant	21/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

96871

AN:

151032

Hom.:

31788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.716

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.748

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.646

GnomAD3 exomes

AF:

0.691

AC:

170335

AN:

246578

Hom.:

59730

AF XY:

0.699

AC XY:

93815

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.719

Gnomad ASJ exome

AF:

0.739

Gnomad EAS exome

AF:

0.617

Gnomad SAS exome

AF:

0.784

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.687

AC:

1004151

AN:

1460928

Hom.:

347364

Cov.:

118

AF XY:

0.692

AC XY:

502599

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.715

Gnomad4 ASJ exome

AF:

0.736

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.776

Gnomad4 FIN exome

AF:

0.668

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.641

AC:

96935

AN:

151148

Hom.:

31805

Cov.:

AF XY:

0.644

AC XY:

47616

AN XY:

73902

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.678

Gnomad4 ASJ

AF:

0.737

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.745

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.689

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.671

Hom.:

14880

Bravo

AF:

0.632

Asia WGS

AF:

0.689

AC:

2397

AN:

3478

EpiCase

AF:

0.703

EpiControl

AF:

0.702

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Vesicoureteral reflux 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Ehlers-Danlos syndrome due to tenascin-X deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 19, 2018

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

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

-0.75

CADD

Benign

0.041

DANN

Benign

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over