rs12196385

Positions:

chr6-32058203-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.7680C>T(p.Asp2560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,612,278 control chromosomes in the GnomAD database, including 7,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 912 hom., cov: 31)

Exomes 𝑓: 0.087 ( 6299 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -7.03

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=-0.91).

BP6

Variant 6-32058203-G-A is Benign according to our data. Variant chr6-32058203-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32058203-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.7680C>T	p.Asp2560=	synonymous_variant	22/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.7680C>T	p.Asp2560=	synonymous_variant	22/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.7680C>T	p.Asp2560=	synonymous_variant	22/44		NM_001365276.2	ENSP00000496448		P22105-3
TNXB	ENST00000647633.1 linkuse as main transcript	c.8421C>T	p.Asp2807=	synonymous_variant	23/45			ENSP00000497649	P1
TNXB	ENST00000375244.7 linkuse as main transcript	c.7680C>T	p.Asp2560=	synonymous_variant	22/44	5		ENSP00000364393		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15366

AN:

151950

Hom.:

917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0538

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0881

Gnomad OTH

AF:

0.0955

GnomAD3 exomes

AF:

0.0818

AC:

20203

AN:

247096

Hom.:

1074

AF XY:

0.0851

AC XY:

11453

AN XY:

134504

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0454

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0335

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0529

Gnomad NFE exome

AF:

0.0810

Gnomad OTH exome

AF:

0.0808

GnomAD4 exome

AF:

0.0870

AC:

127073

AN:

1460210

Hom.:

6299

Cov.:

AF XY:

0.0879

AC XY:

63838

AN XY:

726408

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.0483

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0211

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.0532

Gnomad4 NFE exome

AF:

0.0862

Gnomad4 OTH exome

AF:

0.0943

GnomAD4 genome

AF:

0.101

AC:

15378

AN:

152068

Hom.:

912

Cov.:

AF XY:

0.0996

AC XY:

7404

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0526

Gnomad4 ASJ

AF:

0.0957

Gnomad4 EAS

AF:

0.0356

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0538

Gnomad4 NFE

AF:

0.0881

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.0947

Hom.:

326

Bravo

AF:

0.104

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

EpiCase

AF:

0.0947

EpiControl

AF:

0.0874

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.91

CADD

Benign

0.32

DANN

Benign

0.68

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