6-32042509-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001365276.2(TNXB):c.12156C>G(p.Arg4052=) 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 0.0039 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0013 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.94

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-32042509-G-C is Benign according to our data. Variant chr6-32042509-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 261119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.94 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.12156C>G	p.Arg4052=	synonymous_variant	40/44	ENST00000644971.2
TNXB	NM_019105.8	c.12150C>G	p.Arg4050=	synonymous_variant	40/44
TNXB	NM_032470.4	c.1443C>G	p.Arg481=	synonymous_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.12156C>G	p.Arg4052=	synonymous_variant	40/44		NM_001365276.2

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 596 AN: 150556 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00441

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00708

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00531

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0319

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.0102

GnomAD3 exomes AF: 0.00166 AC: 408 AN: 245372 Hom.: 8 AF XY: 0.00184 AC XY: 245 AN XY: 132886

Gnomad AFR exome AF: 0.00349

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.000889

Gnomad SAS exome AF: 0.00209

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.00201

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00128 AC: 1850 AN: 1441036 Hom.: 13 Cov.: 33 AF XY: 0.00145 AC XY: 1037 AN XY: 716456

Gnomad4 AFR exome AF: 0.00211

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.00355

Gnomad4 EAS exome AF: 0.00147

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.000191

Gnomad4 NFE exome AF: 0.000962

Gnomad4 OTH exome AF: 0.00243

GnomAD4 genome AF: 0.00394 AC: 593 AN: 150684 Hom.: 0 Cov.: 20 AF XY: 0.00405 AC XY: 298 AN XY: 73636

Gnomad4 AFR AF: 0.00439

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00708

Gnomad4 EAS AF: 0.00158

Gnomad4 SAS AF: 0.00531

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.0101

Alfa AF: 0.00442 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ehlers-Danlos syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 01, 2019

- -

Ehlers-Danlos syndrome due to tenascin-X deficiency;C4014831:Vesicoureteral reflux 8 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	3.5
Dann	Benign	0.79

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: rs6457479; hg19: chr6-32010286;