chr6-32074545-T-C

Variant names:

• chr6-32074545-T-C
• rs3130286
• NM_001365276.2:c.4376-593A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365276.2(TNXB):​c.4376-593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,086 control chromosomes in the GnomAD database, including 51,599 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 0.82 (51599 hom., cov: 30)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 21 publications found

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]

TNXB Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome due to tenascin-X deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina, PanelApp Australia, Orphanet
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• vesicoureteral reflux 8

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000294466 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.4376-593A>G		intron_variant	Intron 11 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.5117-593A>G		intron_variant	Intron 12 of 44		NP_001415264.1
TNXB	NM_019105.8	c.4376-593A>G		intron_variant	Intron 11 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.4376-593A>G		intron_variant	Intron 11 of 43		NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.5117-593A>G		intron_variant	Intron 12 of 44			ENSP00000497649.1
TNXB	ENST00000375244.7	c.4376-593A>G		intron_variant	Intron 11 of 43	5		ENSP00000364393.3
ENSG00000294466	ENST00000723790.1	n.163-1909T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124815 AN: 151968 Hom.: 51552 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.821 AC: 124918 AN: 152086 Hom.: 51599 Cov.: 30 AF XY: 0.823 AC XY: 61156 AN XY: 74342

African (AFR) AF: 0.890 AC: 36903 AN: 41486

American (AMR) AF: 0.854 AC: 13057 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3084 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3775 AN: 5162

South Asian (SAS) AF: 0.800 AC: 3846 AN: 4810

European-Finnish (FIN) AF: 0.827 AC: 8743 AN: 10578

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52745 AN: 67970

Other (OTH) AF: 0.832 AC: 1758 AN: 2112

Alfa AF: 0.796 Hom.: 130970

Bravo AF: 0.830

Asia WGS AF: 0.757 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3130286; hg19: chr6-32042322;