rs190967484

Positions:

chr6-32072132-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001365276.2(TNXB):c.4848G>A(p.Gly1616=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,086 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.010 ( 116 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.688

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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 6-32072132-C-T is Benign according to our data. Variant chr6-32072132-C-T is described in ClinVar as [Benign]. Clinvar id is 261139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32072132-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.688 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 16 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.4848G>A	p.Gly1616=	synonymous_variant	13/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.4848G>A	p.Gly1616=	synonymous_variant	13/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.4848G>A	p.Gly1616=	synonymous_variant	13/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.5589G>A	p.Gly1863=	synonymous_variant	14/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.4848G>A	p.Gly1616=	synonymous_variant	13/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1534

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0293

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.0101

AC:

2514

AN:

247782

Hom.:

AF XY:

0.0105

AC XY:

1415

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.000390

Gnomad SAS exome

AF:

0.00521

Gnomad FIN exome

AF:

0.0260

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.0105

AC:

15295

AN:

1460804

Hom.:

116

Cov.:

AF XY:

0.0106

AC XY:

7684

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00424

Gnomad4 ASJ exome

AF:

0.0347

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00501

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00883

GnomAD4 genome

AF:

0.0101

AC:

1534

AN:

152282

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

823

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.0293

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.00755

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.00950

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 23, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	TNXB: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Ehlers-Danlos syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 27, 2022

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2018

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

-0.42

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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