rs17421133

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365276.2(TNXB):c.12170A>T(p.Asn4057Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,610,306 control chromosomes in the GnomAD database, including 78,750 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6422 hom., cov: 23)

Exomes 𝑓: 0.31 ( 72328 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.00500

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004891485).

BP6

Variant 6-32042495-T-A is Benign according to our data. Variant chr6-32042495-T-A is described in ClinVar as [Benign]. Clinvar id is 261120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32042495-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.12170A>T	p.Asn4057Ile	missense_variant	Exon 40 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12911A>T	p.Asn4304Ile	missense_variant	Exon 41 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.12164A>T	p.Asn4055Ile	missense_variant	Exon 40 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 link	c.1457A>T	p.Asn486Ile	missense_variant	Exon 9 of 13		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.12170A>T	p.Asn4057Ile	missense_variant	Exon 40 of 44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38708

AN:

151314

Hom.:

6412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.253

GnomAD3 exomes

AF:

0.320

AC:

79846

AN:

249888

Hom.:

14563

AF XY:

0.319

AC XY:

43100

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.305

AC:

445066

AN:

1458874

Hom.:

72328

Cov.:

AF XY:

0.306

AC XY:

221805

AN XY:

725826

show subpopulations

Gnomad4 AFR exome

AF:

0.0506

Gnomad4 AMR exome

AF:

0.443

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.256

AC:

38724

AN:

151432

Hom.:

6422

Cov.:

AF XY:

0.261

AC XY:

19311

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.383

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.318

Hom.:

2585

Bravo

AF:

0.249

ESP6500AA

AF:

0.0754

AC:

228

ESP6500EA

AF:

0.315

AC:

1707

ExAC

AF:

0.308

AC:

37441

Asia WGS

AF:

0.226

AC:

787

AN:

3474

EpiCase

AF:

0.342

EpiControl

AF:

0.353

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome due to tenascin-X deficiency

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Vesicoureteral reflux 8

Benign:1

Sep 10, 2021

Genome-Nilou Lab

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 17, 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

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.081

.;.;.;.;T

Eigen

Benign

-0.023

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.038

.;T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T;T

MetaSVM

Benign

-0.74

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

.;.;D;D;.

REVEL

Benign

0.23

Sift

Benign

0.071

.;.;T;D;.

Sift4G

Uncertain

0.025

.;.;D;T;T

Vest4

0.41, 0.33

MPC

0.42

ClinPred

0.025

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.42

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