6-32058330-C-T

Position:

chr6-32058330-C-T

Variant summary

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

The NM_001365276.2(TNXB):c.7553G>A(p.Gly2518Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,611,184 control chromosomes in the GnomAD database, including 409,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36743 hom., cov: 31)

Exomes 𝑓: 0.71 ( 372537 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.350

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=9.462437E-7).

BP6

Variant 6-32058330-C-T is Benign according to our data. Variant chr6-32058330-C-T is described in ClinVar as [Benign]. Clinvar id is 261162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32058330-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.75 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.7553G>A	p.Gly2518Glu	missense_variant	22/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.7553G>A	p.Gly2518Glu	missense_variant	22/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.7553G>A	p.Gly2518Glu	missense_variant	22/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.8294G>A	p.Gly2765Glu	missense_variant	23/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.7553G>A	p.Gly2518Glu	missense_variant	22/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

104635

AN:

151308

Hom.:

36712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.722

GnomAD3 exomes

AF:

0.720

AC:

173470

AN:

240990

Hom.:

63139

AF XY:

0.724

AC XY:

95859

AN XY:

132356

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.617

Gnomad SAS exome

AF:

0.783

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.724

GnomAD4 exome

AF:

0.713

AC:

1040295

AN:

1459760

Hom.:

372537

Cov.:

AF XY:

0.716

AC XY:

519633

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.647

Gnomad4 AMR exome

AF:

0.783

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.775

Gnomad4 FIN exome

AF:

0.648

Gnomad4 NFE exome

AF:

0.709

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.692

AC:

104717

AN:

151424

Hom.:

36743

Cov.:

AF XY:

0.691

AC XY:

51152

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.635

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.852

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.746

Gnomad4 FIN

AF:

0.651

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.719

Alfa

AF:

0.711

Hom.:

13846

Bravo

AF:

0.699

TwinsUK

AF:

0.714

AC:

2647

ALSPAC

AF:

0.710

AC:

2736

ESP6500AA

AF:

0.652

AC:

1507

ESP6500EA

AF:

0.701

AC:

3513

ExAC

AF:

0.714

AC:

83884

Asia WGS

AF:

0.693

AC:

2414

AN:

3478

EpiCase

AF:

0.730

EpiControl

AF:

0.732

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Ehlers-Danlos syndrome due to tenascin-X deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Vesicoureteral reflux 8

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 07, 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

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.077

DANN

Benign

0.16

DEOGEN2

Benign

0.022

T;.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00094

LIST_S2

Benign

0.034

.;T;T;T

MetaRNN

Benign

9.5e-7

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

2.3

.;.;N;.

REVEL

Benign

0.024

Sift

Benign

1.0

.;.;T;.

Sift4G

Benign

1.0

.;.;T;T

Vest4

0.025

ClinPred

0.0011

GERP RS

3.3

Varity_R

0.025

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