6-32043458-C-T

Variant names:

Variant summary

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

The NM_001365276.2(TNXB):c.11629G>A(p.Val3877Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 7338 hom., cov: 8)

Exomes 𝑓: 0.51 ( 68106 hom. )

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.115

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=1.1128426E-5).

BP6

Variant 6-32043458-C-T is Benign according to our data. Variant chr6-32043458-C-T is described in ClinVar as [Benign]. Clinvar id is 261114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32043458-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.11629G>A	p.Val3877Ile	missense_variant	Exon 36 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12370G>A	p.Val4124Ile	missense_variant	Exon 37 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.11623G>A	p.Val3875Ile	missense_variant	Exon 36 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 link	c.916G>A	p.Val306Ile	missense_variant	Exon 5 of 13		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.11629G>A	p.Val3877Ile	missense_variant	Exon 36 of 44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

29244

AN:

62378

Hom.:

7336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.516

AC:

45116

AN:

87412

Hom.:

12067

AF XY:

0.515

AC XY:

23374

AN XY:

45364

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.639

Gnomad EAS exome

AF:

0.370

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.480

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.511

AC:

259498

AN:

507536

Hom.:

68106

Cov.:

AF XY:

0.518

AC XY:

138501

AN XY:

267406

show subpopulations

Gnomad4 AFR exome

AF:

0.452

Gnomad4 AMR exome

AF:

0.598

Gnomad4 ASJ exome

AF:

0.648

Gnomad4 EAS exome

AF:

0.452

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.469

AC:

29274

AN:

62454

Hom.:

7338

Cov.:

AF XY:

0.472

AC XY:

12918

AN XY:

27370

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.565

Gnomad4 FIN

AF:

0.477

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.504

Hom.:

3489

Bravo

AF:

0.501

ExAC

AF:

0.335

AC:

20900

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.033

T;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.60

.;T;T;T;T

MetaRNN

Benign

0.000011

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.45

.;.;N;N;.

REVEL

Benign

0.033

Sift

Benign

0.62

.;.;T;T;.

Sift4G

Benign

0.17

.;.;T;T;T

Vest4

0.031, 0.056

MPC

0.28

ClinPred

0.00073

GERP RS

0.73

Varity_R

0.028

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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