rs117182156

Positions:

chr6-32089371-C-T

Variant summary

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

The NM_001365276.2(TNXB):c.2367G>A(p.Gly789=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,605,796 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 102 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.917

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=-0.67).

BP6

Variant 6-32089371-C-T is Benign according to our data. Variant chr6-32089371-C-T is described in ClinVar as [Benign]. Clinvar id is 261129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32089371-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.917 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00525 (7624/1453470) while in subpopulation EAS AF= 0.04 (1586/39614). AF 95% confidence interval is 0.0384. There are 102 homozygotes in gnomad4_exome. There are 4074 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.2367G>A	p.Gly789=	synonymous_variant	5/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.2367G>A	p.Gly789=	synonymous_variant	5/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.2367G>A	p.Gly789=	synonymous_variant	5/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.2367G>A	p.Gly789=	synonymous_variant	5/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.2367G>A	p.Gly789=	synonymous_variant	5/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

711

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00645

AC:

1562

AN:

242334

Hom.:

AF XY:

0.00721

AC XY:

949

AN XY:

131608

show subpopulations

Gnomad AFR exome

AF:

0.000272

Gnomad AMR exome

AF:

0.00444

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.0115

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.000530

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00525

AC:

7624

AN:

1453470

Hom.:

102

Cov.:

AF XY:

0.00564

AC XY:

4074

AN XY:

722380

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0400

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.000751

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00649

GnomAD4 genome

AF:

0.00466

AC:

710

AN:

152326

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

385

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00485

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00657

Hom.:

Bravo

AF:

0.00485

Asia WGS

AF:

0.0110

AC:

AN:

3478

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 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	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

Feb 08, 2022

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2019

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

-0.67

CADD

Benign

5.3

DANN

Benign

0.57

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