rs3749962

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.6030C>T(p.Pro2010Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,830 control chromosomes in the GnomAD database, including 15,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2202 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12905 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.11

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-32068580-G-A is Benign according to our data. Variant chr6-32068580-G-A is described in ClinVar as [Benign]. Clinvar id is 261144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32068580-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.6030C>T	p.Pro2010Pro	synonymous_variant	Exon 17 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.6771C>T	p.Pro2257Pro	synonymous_variant	Exon 18 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.6030C>T	p.Pro2010Pro	synonymous_variant	Exon 17 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.6030C>T	p.Pro2010Pro	synonymous_variant	Exon 17 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.6771C>T	p.Pro2257Pro	synonymous_variant	Exon 18 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.6030C>T	p.Pro2010Pro	synonymous_variant	Exon 17 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22622

AN:

152080

Hom.:

2191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.0964

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.139

AC:

34695

AN:

249064

Hom.:

3580

AF XY:

0.151

AC XY:

20381

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0961

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.351

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.111

AC:

162908

AN:

1461632

Hom.:

12905

Cov.:

AF XY:

0.119

AC XY:

86584

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.0685

Gnomad4 NFE exome

AF:

0.0901

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.149

AC:

22656

AN:

152198

Hom.:

2202

Cov.:

AF XY:

0.152

AC XY:

11315

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.0964

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.117

Hom.:

641

Bravo

AF:

0.155

Asia WGS

AF:

0.247

AC:

862

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

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 31, 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

-0.82

CADD

Benign

0.98

DANN

Benign

0.43

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