6-32064966-G-A

Position:

chr6-32064966-G-A

Variant summary

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

The NM_001365276.2(TNXB):c.6696C>T(p.Asp2232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,612,086 control chromosomes in the GnomAD database, including 133,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11883 hom., cov: 31)

Exomes 𝑓: 0.40 ( 122050 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.29

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=-0.86).

BP6

Variant 6-32064966-G-A is Benign according to our data. Variant chr6-32064966-G-A is described in ClinVar as [Benign]. Clinvar id is 261150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32064966-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.6696C>T	p.Asp2232=	synonymous_variant	19/44	ENST00000644971.2
TNXB	NM_019105.8 linkuse as main transcript	c.6696C>T	p.Asp2232=	synonymous_variant	19/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.6696C>T	p.Asp2232=	synonymous_variant	19/44		NM_001365276.2		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.7437C>T	p.Asp2479=	synonymous_variant	20/45			P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.6696C>T	p.Asp2232=	synonymous_variant	19/44	5			P22105-3

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57919

AN:

151920

Hom.:

11874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.438

AC:

106625

AN:

243534

Hom.:

24451

AF XY:

0.435

AC XY:

58028

AN XY:

133270

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.451

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.404

AC:

589342

AN:

1460048

Hom.:

122050

Cov.:

AF XY:

0.405

AC XY:

294009

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.381

AC:

57948

AN:

152038

Hom.:

11883

Cov.:

AF XY:

0.387

AC XY:

28749

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.400

Hom.:

5470

Bravo

AF:

0.378

Asia WGS

AF:

0.380

AC:

1323

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Vesicoureteral reflux 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Ehlers-Danlos syndrome due to tenascin-X deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 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

-0.86

CADD

Benign

0.069

DANN

Benign

0.67

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