rs61740337

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365276.2(TNXB):c.9699T>C(p.His3233His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,612,390 control chromosomes in the GnomAD database, including 3,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 286 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3114 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.996

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-32049328-A-G is Benign according to our data. Variant chr6-32049328-A-G is described in ClinVar as [Benign]. Clinvar id is 261182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32049328-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.9699T>C	p.His3233His	synonymous_variant	Exon 28 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.10440T>C	p.His3480His	synonymous_variant	Exon 29 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.9693T>C	p.His3231His	synonymous_variant	Exon 28 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.9699T>C	p.His3233His	synonymous_variant	Exon 28 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.10440T>C	p.His3480His	synonymous_variant	Exon 29 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.9699T>C	p.His3233His	synonymous_variant	Exon 28 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7419

AN:

152058

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0991

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0581

AC:

14337

AN:

246932

Hom.:

565

AF XY:

0.0588

AC XY:

7895

AN XY:

134310

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0618

AC:

90172

AN:

1460214

Hom.:

3114

Cov.:

AF XY:

0.0613

AC XY:

44524

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.00951

Gnomad4 AMR exome

AF:

0.0342

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.0777

Gnomad4 SAS exome

AF:

0.0571

Gnomad4 FIN exome

AF:

0.0624

Gnomad4 NFE exome

AF:

0.0651

Gnomad4 OTH exome

AF:

0.0672

GnomAD4 genome

AF:

0.0488

AC:

7432

AN:

152176

Hom.:

286

Cov.:

AF XY:

0.0490

AC XY:

3644

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0345

Gnomad4 ASJ

AF:

0.0162

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.0746

Gnomad4 FIN

AF:

0.0603

Gnomad4 NFE

AF:

0.0658

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.0548

Hom.:

135

Bravo

AF:

0.0439

Asia WGS

AF:

0.144

AC:

499

AN:

3478

EpiCase

AF:

0.0532

EpiControl

AF:

0.0582

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 17, 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

-0.55

CADD

Benign

3.9

DANN

Benign

0.29

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