rs2239689

Positions:

• chr6-32062507-G-A

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.6842-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,564,790 control chromosomes in the GnomAD database, including 75,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6432 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69187 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.391

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=-0.9).
• BP6: Variant 6-32062507-G-A is Benign according to our data. Variant chr6-32062507-G-A is described in ClinVar as [Benign]. Clinvar id is 261152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.6842-24C>T		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.6842-24C>T		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.6842-24C>T		intron_variant			NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.7583-24C>T		intron_variant				ENSP00000497649.1
TNXB	ENST00000375244.7	c.6842-24C>T		intron_variant		5		ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39048 AN: 151926 Hom.: 6425 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.335 AC: 62709 AN: 187348 Hom.: 11354 AF XY: 0.332 AC XY: 33659 AN XY: 101496

Gnomad AFR exome AF: 0.0550

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.305 AC: 431406 AN: 1412746 Hom.: 69187 Cov.: 33 AF XY: 0.306 AC XY: 213101 AN XY: 696814

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.257 AC: 39061 AN: 152044 Hom.: 6432 Cov.: 32 AF XY: 0.263 AC XY: 19527 AN XY: 74296

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.253

Alfa AF: 0.331 Hom.: 11840

Bravo AF: 0.249

Asia WGS AF: 0.227 AC: 790 AN: 3478

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	-0.90
CADD	Benign	3.3
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2239689; hg19: chr6-32030284; COSMIC: COSV64476182; COSMIC: COSV64476182;