rs2856451

Positions:

• chr6-32043581-A-G
• chr6-32043581-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365276.2(TNXB):​c.11531-25T>C variant causes a intron 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (19762 hom., cov: 15)
  • Exomes 𝑓: 0.55 (151469 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.768

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-32043581-A-G is Benign according to our data. Variant chr6-32043581-A-G is described in ClinVar as [Benign]. Clinvar id is 261111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32043581-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.11531-25T>C		intron_variant		ENST00000644971.2
TNXB	NM_019105.8	c.11525-25T>C		intron_variant
TNXB	NM_032470.4	c.818-25T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.11531-25T>C		intron_variant			NM_001365276.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 70365 AN: 128312 Hom.: 19733 Cov.: 15

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.578

GnomAD3 exomes AF: 0.591 AC: 131899 AN: 223084 Hom.: 39743 AF XY: 0.597 AC XY: 73735 AN XY: 123508

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.664

Gnomad ASJ exome AF: 0.769

Gnomad EAS exome AF: 0.414

Gnomad SAS exome AF: 0.669

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.601

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.549 AC: 538049 AN: 979198 Hom.: 151469 Cov.: 13 AF XY: 0.557 AC XY: 281138 AN XY: 504758

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.549 AC: 70450 AN: 128428 Hom.: 19762 Cov.: 15 AF XY: 0.556 AC XY: 34253 AN XY: 61590

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.583

Alfa AF: 0.522 Hom.: 2657

Bravo AF: 0.550

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Vesicoureteral reflux 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Ehlers-Danlos syndrome due to tenascin-X deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	17
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs2856451; hg19: chr6-32011358;