Variant rs374698 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.11142G>A(p.Thr3714=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 38 hom., cov: 4)

Exomes 𝑓: 0.050 ( 484 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -10.3

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-32044502-C-T is Benign according to our data. Variant chr6-32044502-C-T is described in ClinVar as [Benign]. Clinvar id is 261102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32044502-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-10.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNXB	NM_001365276.2 linkuse as main transcript	c.11142G>A	p.Thr3714=	synonymous_variant	33/44	ENST00000644971.2
TNXB	NM_019105.8 linkuse as main transcript	c.11136G>A	p.Thr3712=	synonymous_variant	33/44
TNXB	NM_032470.4 linkuse as main transcript	c.429G>A	p.Thr143=	synonymous_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.11142G>A	p.Thr3714=	synonymous_variant	33/44		NM_001365276.2		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

716

AN:

15778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.0814

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.0239

Gnomad FIN

AF:

0.00234

Gnomad MID

AF:

0.0682

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0612

AC:

2929

AN:

47852

Hom.:

AF XY:

0.0608

AC XY:

1475

AN XY:

24260

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0519

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.0607

Gnomad SAS exome

AF:

0.0259

Gnomad FIN exome

AF:

0.00765

Gnomad NFE exome

AF:

0.0646

Gnomad OTH exome

AF:

0.0711

GnomAD4 exome

AF:

0.0498

AC:

18574

AN:

372862

Hom.:

484

Cov.:

AF XY:

0.0479

AC XY:

9408

AN XY:

196380

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.0535

Gnomad4 EAS exome

AF:

0.0564

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.0539

Gnomad4 OTH exome

AF:

0.0524

GnomAD4 genome

AF:

0.0456

AC:

720

AN:

15782

Hom.:

Cov.:

AF XY:

0.0450

AC XY:

289

AN XY:

6418

show subpopulations

Gnomad4 AFR

AF:

0.0807

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.0322

Gnomad4 SAS

AF:

0.0241

Gnomad4 FIN

AF:

0.00234

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0542

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Feb 24, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.027

DANN

Benign

0.94

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