chr6-32058086-C-T

Variant names:

Variant summary

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

The NM_001365276.2(TNXB):c.7797G>A(p.Leu2599Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,610,946 control chromosomes in the GnomAD database, including 17,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 937 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16286 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.21

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=-0.52).

BP6

Variant 6-32058086-C-T is Benign according to our data. Variant chr6-32058086-C-T is described in ClinVar as [Benign]. Clinvar id is 261165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32058086-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.7797G>A	p.Leu2599Leu	synonymous_variant	Exon 22 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.8538G>A	p.Leu2846Leu	synonymous_variant	Exon 23 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.7797G>A	p.Leu2599Leu	synonymous_variant	Exon 22 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.7797G>A	p.Leu2599Leu	synonymous_variant	Exon 22 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.8538G>A	p.Leu2846Leu	synonymous_variant	Exon 23 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.7797G>A	p.Leu2599Leu	synonymous_variant	Exon 22 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0989

AC:

15040

AN:

152140

Hom.:

935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0559

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.0780

GnomAD3 exomes

AF:

0.0908

AC:

22249

AN:

244988

Hom.:

1419

AF XY:

0.0898

AC XY:

11996

AN XY:

133562

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.0531

Gnomad EAS exome

AF:

0.0144

Gnomad SAS exome

AF:

0.0293

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.0918

GnomAD4 exome

AF:

0.139

AC:

202166

AN:

1458688

Hom.:

16286

Cov.:

AF XY:

0.135

AC XY:

97956

AN XY:

725390

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.0433

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.0185

Gnomad4 SAS exome

AF:

0.0268

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.0988

AC:

15046

AN:

152258

Hom.:

937

Cov.:

AF XY:

0.0935

AC XY:

6961

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0558

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0184

Gnomad4 SAS

AF:

0.0273

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.0772

Alfa

AF:

0.123

Hom.:

570

Bravo

AF:

0.0917

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 11, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.52

CADD

Benign

2.5

DANN

Benign

0.55

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