chr6-32062152-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001365276.2(TNXB):c.7168+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0364 in 1,609,336 control chromosomes in the GnomAD database, including 1,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 189 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1150 hom. )

Consequence

TNXB
NM_001365276.2 splice_region, intron

Scores

Splicing: ADA: 0.9956

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.37

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 Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 6-32062152-C-T is Benign according to our data. Variant chr6-32062152-C-T is described in ClinVar as [Benign]. Clinvar id is 261154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32062152-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.7168+5G>A	splice_region_variant, intron_variant	Intron 20 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.7909+5G>A	splice_region_variant, intron_variant	Intron 21 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.7168+5G>A	splice_region_variant, intron_variant	Intron 20 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.7168+5G>A	splice_region_variant, intron_variant	Intron 20 of 43		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.7909+5G>A	splice_region_variant, intron_variant	Intron 21 of 44			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.7168+5G>A	splice_region_variant, intron_variant	Intron 20 of 43	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6579

AN:

152232

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0480

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0251

AC:

6118

AN:

243866

Hom.:

129

AF XY:

0.0233

AC XY:

3099

AN XY:

133024

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000297

Gnomad FIN exome

AF:

0.00369

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0357

AC:

52050

AN:

1456986

Hom.:

1150

Cov.:

AF XY:

0.0338

AC XY:

24476

AN XY:

724008

show subpopulations

Gnomad4 AFR exome

AF:

0.0794

Gnomad4 AMR exome

AF:

0.0356

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000291

Gnomad4 FIN exome

AF:

0.00429

Gnomad4 NFE exome

AF:

0.0407

Gnomad4 OTH exome

AF:

0.0338

GnomAD4 genome

AF:

0.0432

AC:

6585

AN:

152350

Hom.:

189

Cov.:

AF XY:

0.0408

AC XY:

3042

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.0480

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.0337

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0364

Hom.:

Bravo

AF:

0.0497

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Jul 14, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 21, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.83

SpliceAI score (max)

0.010

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