Variant 6-32041864-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001365276.2(TNXB):c.12540C>T(p.Ile4180=) 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 0.00093 ( 0 hom., cov: 13)

Exomes 𝑓: 0.0011 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 6-32041864-G-A is Benign according to our data. Variant chr6-32041864-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656439.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32041864-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNXB	NM_001365276.2 linkuse as main transcript	c.12540C>T	p.Ile4180=	synonymous_variant	43/44	ENST00000644971.2
TNXB	NM_019105.8 linkuse as main transcript	c.12534C>T	p.Ile4178=	synonymous_variant	43/44
TNXB	NM_032470.4 linkuse as main transcript	c.1827C>T	p.Ile609=	synonymous_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.12540C>T	p.Ile4180=	synonymous_variant	43/44		NM_001365276.2		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

101

AN:

108092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000842

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000871

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00157

Gnomad OTH

AF:

0.000718

GnomAD3 exomes

AF:

0.000745

AC:

AN:

126194

Hom.:

AF XY:

0.000704

AC XY:

AN XY:

68190

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.000650

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00123

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.000520

GnomAD4 exome

AF:

0.00114

AC:

703

AN:

618600

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

339

AN XY:

326068

show subpopulations

Gnomad4 AFR exome

AF:

0.000283

Gnomad4 AMR exome

AF:

0.000565

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000311

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.000934

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000933

AC:

101

AN:

108204

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

AN XY:

51222

show subpopulations

Gnomad4 AFR

AF:

0.000182

Gnomad4 AMR

AF:

0.000840

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000871

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.000708

Alfa

AF:

0.000144

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

TNXB: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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