rs10947230

Positions:

chr6-32056618-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.8111G>A(p.Arg2704His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,612,948 control chromosomes in the GnomAD database, including 4,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 930 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3683 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.27

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=0.001785636).

BP6

Variant 6-32056618-C-T is Benign according to our data. Variant chr6-32056618-C-T is described in ClinVar as [Benign]. Clinvar id is 261166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32056618-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 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.8111G>A	p.Arg2704His	missense_variant	23/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.8111G>A	p.Arg2704His	missense_variant	23/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.8111G>A	p.Arg2704His	missense_variant	23/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.8852G>A	p.Arg2951His	missense_variant	24/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.8111G>A	p.Arg2704His	missense_variant	23/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14913

AN:

152162

Hom.:

928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0724

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.0832

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0856

GnomAD3 exomes

AF:

0.0778

AC:

19093

AN:

245378

Hom.:

1034

AF XY:

0.0726

AC XY:

9727

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0923

Gnomad ASJ exome

AF:

0.00964

Gnomad EAS exome

AF:

0.0888

Gnomad SAS exome

AF:

0.0323

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.0622

Gnomad OTH exome

AF:

0.0649

GnomAD4 exome

AF:

0.0642

AC:

93775

AN:

1460668

Hom.:

3683

Cov.:

AF XY:

0.0626

AC XY:

45515

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0851

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0718

Gnomad4 SAS exome

AF:

0.0336

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0597

Gnomad4 OTH exome

AF:

0.0590

GnomAD4 genome

AF:

0.0980

AC:

14920

AN:

152280

Hom.:

930

Cov.:

AF XY:

0.100

AC XY:

7454

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.0721

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.0829

Gnomad4 SAS

AF:

0.0395

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.0852

Alfa

AF:

0.0635

Hom.:

325

Bravo

AF:

0.0948

TwinsUK

AF:

0.0572

AC:

212

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.158

AC:

393

ESP6500EA

AF:

0.0620

AC:

314

ExAC

AF:

0.0767

AC:

9227

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

EpiCase

AF:

0.0643

EpiControl

AF:

0.0615

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2018

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 24, 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

0.17

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

.;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.63

P;P

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.2

.;.;D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0060

.;.;D;.

Sift4G

Pathogenic

0.0

.;.;D;D

Vest4

0.18

ClinPred

0.023

GERP RS

4.6

Varity_R

0.21

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