rs2894232

chr6-32043867-A-Gchr6-32043867-A-T

Variant summary

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

The NM_001365276.2(TNXB):c.11412T>C(p.Asp3804=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,612,924 control chromosomes in the GnomAD database, including 13,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1891 hom., cov: 27)

Exomes 𝑓: 0.12 ( 11872 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.91

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=-0.95).

BP6

Variant 6-32043867-A-G is Benign according to our data. Variant chr6-32043867-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32043867-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNXB	NM_001365276.2 linkuse as main transcript	c.11412T>C	p.Asp3804=	synonymous_variant	35/44	ENST00000644971.2
TNXB	NM_019105.8 linkuse as main transcript	c.11406T>C	p.Asp3802=	synonymous_variant	35/44
TNXB	NM_032470.4 linkuse as main transcript	c.699T>C	p.Asp233=	synonymous_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.11412T>C	p.Asp3804=	synonymous_variant	35/44		NM_001365276.2		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22110

AN:

151630

Hom.:

1883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0756

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.138

AC:

34759

AN:

251186

Hom.:

2955

AF XY:

0.143

AC XY:

19451

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.0809

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.117

AC:

170645

AN:

1461176

Hom.:

11872

Cov.:

AF XY:

0.121

AC XY:

87866

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.0838

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.146

AC:

22142

AN:

151748

Hom.:

1891

Cov.:

AF XY:

0.148

AC XY:

10944

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.0756

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.120

Hom.:

647

Bravo

AF:

0.152

Asia WGS

AF:

0.257

AC:

896

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.111

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

Cadd

Benign

0.016

Dann

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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