Variant rs4711283 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.11547A>G(p.Thr3849=) 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 267 hom., cov: 13)

Exomes 𝑓: 0.067 ( 3017 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.204

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=-0.58).

BP6

Variant 6-32043540-T-C is Benign according to our data. Variant chr6-32043540-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.204 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNXB	NM_001365276.2 linkuse as main transcript	c.11547A>G	p.Thr3849=	synonymous_variant	36/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.11541A>G	p.Thr3847=	synonymous_variant	36/44		NP_061978.6
TNXB	NM_032470.4 linkuse as main transcript	c.834A>G	p.Thr278=	synonymous_variant	5/13		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.11547A>G	p.Thr3849=	synonymous_variant	36/44		NM_001365276.2	ENSP00000496448		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

7266

AN:

121526

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.0155

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.0777

Gnomad NFE

AF:

0.0507

Gnomad OTH

AF:

0.0688

GnomAD3 exomes

AF:

0.0820

AC:

15854

AN:

193266

Hom.:

909

AF XY:

0.0872

AC XY:

9324

AN XY:

106958

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.0575

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0729

GnomAD4 exome

AF:

0.0675

AC:

55769

AN:

826264

Hom.:

3017

Cov.:

AF XY:

0.0724

AC XY:

31164

AN XY:

430486

show subpopulations

Gnomad4 AFR exome

AF:

0.0704

Gnomad4 AMR exome

AF:

0.0591

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.0597

Gnomad4 NFE exome

AF:

0.0468

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.0600

AC:

7296

AN:

121638

Hom.:

267

Cov.:

AF XY:

0.0619

AC XY:

3579

AN XY:

57784

show subpopulations

Gnomad4 AFR

AF:

0.0677

Gnomad4 AMR

AF:

0.0558

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.0507

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0590

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.8

DANN

Benign

0.70

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