rs773540524

Positions:

• chr6-32045345-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000451343.4(TNXB):​c.-126C>A variant causes a 5 prime UTR 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 0.0097 (0 hom., cov: 19)
  • Exomes 𝑓: 0.013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB ENST00000451343.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.228

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-32045345-G-T is Benign according to our data. Variant chr6-32045345-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 261096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32045345-G-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.10607-19C>A		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_032470.4	c.-126C>A		5_prime_UTR_variant	1/13		NP_115859.2
TNXB	NM_019105.8	c.10601-19C>A		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.10607-19C>A		intron_variant			NM_001365276.2	ENSP00000496448

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1403 AN: 145140 Hom.: 0 Cov.: 19 FAILED QC

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0229

Gnomad AMR AF: 0.00750

Gnomad ASJ AF: 0.00381

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00174

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00722

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0128 AC: 14808 AN: 1160006 Hom.: 0 Cov.: 18 AF XY: 0.0126 AC XY: 7199 AN XY: 572950

Gnomad4 AFR exome AF: 0.00198

Gnomad4 AMR exome AF: 0.00590

Gnomad4 ASJ exome AF: 0.00537

Gnomad4 EAS exome AF: 0.000257

Gnomad4 SAS exome AF: 0.00264

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00966 AC: 1403 AN: 145258 Hom.: 0 Cov.: 19 AF XY: 0.00951 AC XY: 672 AN XY: 70654

Gnomad4 AFR AF: 0.00211

Gnomad4 AMR AF: 0.00749

Gnomad4 ASJ AF: 0.00381

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00175

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00714

Alfa AF: 0.0143 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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

Apr 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773540524; hg19: chr6-32013122;