6-32058093-C-T

Position:

chr6-32058093-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.7790G>A(p.Arg2597Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,611,260 control chromosomes in the GnomAD database, including 15,087 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 0.14 ( 1903 hom., cov: 32)

Exomes 𝑓: 0.11 ( 13184 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.852

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=0.0046560466).

BP6

Variant 6-32058093-C-T is Benign according to our data. Variant chr6-32058093-C-T is described in ClinVar as [Benign]. Clinvar id is 261164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32058093-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 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.7790G>A	p.Arg2597Gln	missense_variant	22/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.7790G>A	p.Arg2597Gln	missense_variant	22/44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.7790G>A	p.Arg2597Gln	missense_variant	22/44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.8531G>A	p.Arg2844Gln	missense_variant	23/45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 linkuse as main transcript	c.7790G>A	p.Arg2597Gln	missense_variant	22/44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21456

AN:

152050

Hom.:

1898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.0960

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.143

AC:

35157

AN:

245316

Hom.:

3614

AF XY:

0.154

AC XY:

20627

AN XY:

133680

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.113

AC:

165180

AN:

1459092

Hom.:

13184

Cov.:

AF XY:

0.121

AC XY:

87643

AN XY:

725670

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.0685

Gnomad4 NFE exome

AF:

0.0899

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.141

AC:

21486

AN:

152168

Hom.:

1903

Cov.:

AF XY:

0.145

AC XY:

10801

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.0626

Gnomad4 NFE

AF:

0.0960

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.0972

Hom.:

446

Bravo

AF:

0.146

TwinsUK

AF:

0.0852

AC:

316

ALSPAC

AF:

0.0957

AC:

369

ESP6500AA

AF:

0.185

AC:

486

ESP6500EA

AF:

0.0880

AC:

453

ExAC

AF:

0.149

AC:

17984

Asia WGS

AF:

0.270

AC:

941

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.104

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

0.060

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.012

DANN

Benign

0.71

DEOGEN2

Benign

0.017

T;.;T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.15

.;T;T;T

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.24

.;.;N;.

REVEL

Benign

0.011

Sift

Benign

0.60

.;.;T;.

Sift4G

Benign

1.0

.;.;T;T

Vest4

0.0070

ClinPred

0.0037

GERP RS

-6.8

Varity_R

0.017

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