rs116701346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001365276.2(TNXB):c.10368C>T(p.Thr3456Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,579,948 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 5 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.07

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=-0.77).

BP6

Variant 6-32046413-G-A is Benign according to our data. Variant chr6-32046413-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00053 (757/1427610) while in subpopulation AFR AF= 0.00915 (302/33002). AF 95% confidence interval is 0.0083. There are 5 homozygotes in gnomad4_exome. There are 364 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.10368C>T	p.Thr3456Thr	synonymous_variant	Exon 31 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.11109C>T	p.Thr3703Thr	synonymous_variant	Exon 32 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.10362C>T	p.Thr3454Thr	synonymous_variant	Exon 31 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.10368C>T	p.Thr3456Thr	synonymous_variant	Exon 31 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000490077.5 link	n.195C>T		non_coding_transcript_exon_variant	Exon 1 of 14	1
TNXB	ENST00000647633.1 link	c.11109C>T	p.Thr3703Thr	synonymous_variant	Exon 32 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.10368C>T	p.Thr3456Thr	synonymous_variant	Exon 31 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00743

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000808

AC:

195

AN:

241284

Hom.:

AF XY:

0.000636

AC XY:

AN XY:

132174

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.000921

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.000408

Gnomad OTH exome

AF:

0.000676

GnomAD4 exome

AF:

0.000530

AC:

757

AN:

1427610

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

364

AN XY:

703546

show subpopulations

Gnomad4 AFR exome

AF:

0.00915

Gnomad4 AMR exome

AF:

0.000543

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.000180

Gnomad4 SAS exome

AF:

0.0000834

Gnomad4 FIN exome

AF:

0.00209

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.000967

GnomAD4 genome

AF:

0.00249

AC:

379

AN:

152338

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00748

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00210

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000437

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TNXB: BP4, BP7, BS2 -

Jan 30, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Sep 24, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jan 17, 2020

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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

-0.77

CADD

Benign

0.18

DANN

Benign

0.65

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