Variant chr6-32044556-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001365276.2(TNXB):c.11088T>A(p.Thr3696Thr) 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 0.18 ( 33 hom., cov: 3)

Exomes 𝑓: 0.24 ( 1170 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 6-32044556-A-T is Benign according to our data. Variant chr6-32044556-A-T is described in ClinVar as [Benign]. Clinvar id is 261101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32044556-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.11088T>A	p.Thr3696Thr	synonymous_variant	33/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.11082T>A	p.Thr3694Thr	synonymous_variant	33/44		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 linkuse as main transcript	c.375T>A	p.Thr125Thr	synonymous_variant	2/13		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.11088T>A	p.Thr3696Thr	synonymous_variant	33/44		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1478

AN:

8170

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.223

AC:

11360

AN:

50910

Hom.:

162

AF XY:

0.223

AC XY:

5734

AN XY:

25758

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.245

AC:

95028

AN:

388208

Hom.:

1170

Cov.:

AF XY:

0.244

AC XY:

49790

AN XY:

203822

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.300

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.180

AC:

1472

AN:

8168

Hom.:

Cov.:

AF XY:

0.177

AC XY:

603

AN XY:

3410

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.0415

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

- -

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

-1.0

CADD

Benign

0.58

DANN

Benign

0.85

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