rs115612382

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001365276.2(TNXB):c.5679G>A(p.Thr1893Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,612,742 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 36 hom., cov: 32)

Exomes 𝑓: 0.011 ( 279 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.71

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=-0.74).

BP6

Variant 6-32069045-C-T is Benign according to our data. Variant chr6-32069045-C-T is described in ClinVar as [Benign]. Clinvar id is 261142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32069045-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.013 (1981/152228) while in subpopulation AMR AF= 0.036 (551/15286). AF 95% confidence interval is 0.0336. There are 36 homozygotes in gnomad4. There are 891 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.5679G>A	p.Thr1893Thr	synonymous_variant	Exon 16 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.6420G>A	p.Thr2140Thr	synonymous_variant	Exon 17 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.5679G>A	p.Thr1893Thr	synonymous_variant	Exon 16 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.5679G>A	p.Thr1893Thr	synonymous_variant	Exon 16 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.6420G>A	p.Thr2140Thr	synonymous_variant	Exon 17 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.5679G>A	p.Thr1893Thr	synonymous_variant	Exon 16 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1974

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00606

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0160

AC:

3901

AN:

244238

Hom.:

118

AF XY:

0.0144

AC XY:

1925

AN XY:

133670

show subpopulations

Gnomad AFR exome

AF:

0.00649

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00184

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0113

AC:

16446

AN:

1460514

Hom.:

279

Cov.:

AF XY:

0.0111

AC XY:

8035

AN XY:

726550

show subpopulations

Gnomad4 AFR exome

AF:

0.00714

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.0969

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00147

Gnomad4 NFE exome

AF:

0.00944

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0130

AC:

1981

AN:

152228

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

891

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00617

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0162

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

Apr 28, 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

Oct 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 12, 2019

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

-0.74

CADD

Benign

0.055

DANN

Benign

0.40

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