chr6-32096321-C-T

Position:

chr6-32096321-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.1532G>A(p.Arg511His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,548,246 control chromosomes in the GnomAD database, including 13,959 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2281 hom., cov: 34)

Exomes 𝑓: 0.11 ( 11678 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.146

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:

TNXB (HGNC:):

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=0.0062685013).

BP6

Variant 6-32096321-C-T is Benign according to our data. Variant chr6-32096321-C-T is described in ClinVar as [Benign]. Clinvar id is 261125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32096321-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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.1532G>A	p.Arg511His	missense_variant	3/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.1532G>A	p.Arg511His	missense_variant	3/44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.1532G>A	p.Arg511His	missense_variant	3/44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22858

AN:

152132

Hom.:

2268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.0623

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.0945

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.147

AC:

21664

AN:

146980

Hom.:

2338

AF XY:

0.161

AC XY:

12992

AN XY:

80586

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.109

AC:

152312

AN:

1395996

Hom.:

11678

Cov.:

AF XY:

0.116

AC XY:

80076

AN XY:

689910

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.0697

Gnomad4 NFE exome

AF:

0.0883

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.150

AC:

22895

AN:

152250

Hom.:

2281

Cov.:

AF XY:

0.153

AC XY:

11409

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.0623

Gnomad4 NFE

AF:

0.0945

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.0996

Hom.:

1401

Bravo

AF:

0.157

TwinsUK

AF:

0.0852

AC:

316

ALSPAC

AF:

0.0947

AC:

365

ESP6500AA

AF:

0.229

AC:

940

ESP6500EA

AF:

0.0855

AC:

694

ExAC

AF:

0.107

AC:

11845

Asia WGS

AF:

0.244

AC:

851

AN:

3478

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

Jul 09, 2018

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 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

0.095

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.032

LIST_S2

Uncertain

0.90

.;D;D;D;D

MetaRNN

Benign

0.0063

T;T;T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

.;.;D;.;D

REVEL

Benign

0.054

Sift

Benign

0.032

.;.;D;.;D

Sift4G

Uncertain

0.0030

.;.;D;D;D

Vest4

0.099, 0.17

ClinPred

0.027

GERP RS

2.3

Varity_R

0.17

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