Variant rs199757950 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001365276.2(TNXB):c.10677A>G(p.Leu3559=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0052 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0250

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-32045256-T-C is Benign according to our data. Variant chr6-32045256-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32045256-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.025 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNXB	NM_001365276.2 linkuse as main transcript	c.10677A>G	p.Leu3559=	synonymous_variant	32/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.10671A>G	p.Leu3557=	synonymous_variant	32/44		NP_061978.6
TNXB	NM_032470.4 linkuse as main transcript	c.-37A>G		5_prime_UTR_variant	1/13		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.10677A>G	p.Leu3559=	synonymous_variant	32/44		NM_001365276.2	ENSP00000496448		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00422

AC:

630

AN:

149466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00493

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00120

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.000381

Gnomad MID

AF:

0.0667

Gnomad NFE

AF:

0.00518

Gnomad OTH

AF:

0.0133

GnomAD3 exomes

AF:

0.00564

AC:

1135

AN:

201068

Hom.:

AF XY:

0.00641

AC XY:

705

AN XY:

110062

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.000375

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.00862

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00518

AC:

7455

AN:

1439300

Hom.:

Cov.:

AF XY:

0.00547

AC XY:

3909

AN XY:

714498

show subpopulations

Gnomad4 AFR exome

AF:

0.00190

Gnomad4 AMR exome

AF:

0.00383

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.000456

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00694

GnomAD4 genome

AF:

0.00417

AC:

624

AN:

149586

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

310

AN XY:

72942

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00493

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00120

Gnomad4 SAS

AF:

0.00810

Gnomad4 FIN

AF:

0.000381

Gnomad4 NFE

AF:

0.00518

Gnomad4 OTH

AF:

0.0127

Alfa

AF:

0.00936

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

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	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	TNXB: BP4, BP7, BS1 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.4

DANN

Benign

0.81

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