Variant 6-32041765-C-CCTCACCTGATG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001365276.2(TNXB):c.12633+5_12633+6insCATCAGGTGAG variant causes a splice donor region, intron change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000050 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TNXB	NM_001365276.2 linkuse as main transcript	c.12633+5_12633+6insCATCAGGTGAG	splice_donor_region_variant, intron_variant	ENST00000644971.2
TNXB	NM_019105.8 linkuse as main transcript	c.12627+5_12627+6insCATCAGGTGAG	splice_donor_region_variant, intron_variant
TNXB	NM_032470.4 linkuse as main transcript	c.1920+5_1920+6insCATCAGGTGAG	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.12633+5_12633+6insCATCAGGTGAG		splice_donor_region_variant, intron_variant			NM_001365276.2		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0000648

AC:

AN:

138966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000732

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000159

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

95346

Hom.:

AF XY:

0.0000604

AC XY:

AN XY:

49692

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000291

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000501

AC:

AN:

659238

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

344828

show subpopulations

Gnomad4 AFR exome

AF:

0.000207

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.000226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000286

Gnomad4 OTH exome

AF:

0.0000589

GnomAD4 genome

AF:

0.0000719

AC:

AN:

139076

Hom.:

Cov.:

AF XY:

0.0000741

AC XY:

AN XY:

67442

show subpopulations

Gnomad4 AFR

AF:

0.000210

Gnomad4 AMR

AF:

0.0000731

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000159

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2019

In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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