rs3130287

Positions:

• chr6-32082767-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365276.2(TNXB):​c.3446-441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,160 control chromosomes in the GnomAD database, including 62,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (62350 hom., cov: 30)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.3446-441G>A		intron_variant		ENST00000644971.2
TNXB	NM_019105.8	c.3446-441G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.3446-441G>A		intron_variant			NM_001365276.2
TNXB	ENST00000375244.7	c.3446-441G>A		intron_variant		5
TNXB	ENST00000647633.1	c.4187-441G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137432 AN: 152042 Hom.: 62286 Cov.: 30

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.927

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.904 AC: 137555 AN: 152160 Hom.: 62350 Cov.: 30 AF XY: 0.905 AC XY: 67292 AN XY: 74370

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.928

Alfa AF: 0.886 Hom.: 53964

Bravo AF: 0.911

Asia WGS AF: 0.939 AC: 3266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.65

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: rs3130287; hg19: chr6-32050544;