Variant chr6-32043592-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001365276.2(TNXB):c.11531-36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,197,180 control chromosomes in the GnomAD database, including 8,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1478 hom., cov: 22)

Exomes 𝑓: 0.10 ( 7412 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.899

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 6-32043592-G-T is Benign according to our data. Variant chr6-32043592-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 261112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32043592-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.11531-36C>A	intron_variant	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12272-36C>A	intron_variant		NP_001415264.1
TNXB	NM_019105.8 link	c.11525-36C>A	intron_variant		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 link	c.818-36C>A	intron_variant		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.11531-36C>A		intron_variant			NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

18460

AN:

141230

Hom.:

1476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.0169

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.133

AC:

30655

AN:

229832

Hom.:

2599

AF XY:

0.139

AC XY:

17595

AN XY:

126796

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.0670

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.103

AC:

108525

AN:

1055838

Hom.:

7412

Cov.:

AF XY:

0.109

AC XY:

58802

AN XY:

541420

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.0995

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.0707

Gnomad4 NFE exome

AF:

0.0806

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.131

AC:

18486

AN:

141342

Hom.:

1478

Cov.:

AF XY:

0.132

AC XY:

8988

AN XY:

68348

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.0594

Gnomad4 NFE

AF:

0.0925

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.0681

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

-0.94

CADD

Benign

1.4

DANN

Benign

0.64

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