rs185819

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001365276.2(TNXB):c.3482A>T(p.His1161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,600,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1161R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

98 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:

ENSG00000294466 (HGNC:):

ENSG00000294466 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1318565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.3482A>T	p.His1161Leu	missense_variant	Exon 9 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.4223A>T	p.His1408Leu	missense_variant	Exon 10 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.3482A>T	p.His1161Leu	missense_variant	Exon 9 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.3482A>T	p.His1161Leu	missense_variant	Exon 9 of 44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000822

AC:

AN:

243330

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000916

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1448720

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.00

AC:

AN:

39492

South Asian (SAS)

AF:

0.0000705

AC:

AN:

85104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104574

Other (OTH)

AF:

0.00

AC:

AN:

59854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151668

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41208

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67898

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

90065

ExAC

AF:

0.00000857

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.15

T;.;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.028

.;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

.;.;N;.

REVEL

Benign

0.080

Sift

Benign

0.12

.;.;T;.

Sift4G

Uncertain

0.011

.;.;D;T

Vest4

0.29

MutPred

0.42

Loss of disorder (P = 0.0578);.;Loss of disorder (P = 0.0578);.;

MVP

0.082

ClinPred

0.086

GERP RS

4.0

Varity_R

0.10

Mutation Taster

=98/2

polymorphism

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over