rs1150758

Variant names:

• chr6-32060372-G-C
• rs1150758
• NM_001365276.2:c.7492+1025C>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.7492+1025C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 146,312 control chromosomes in the GnomAD database, including 980 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 0.10 (980 hom., cov: 32)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 24 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.7492+1025C>G		intron_variant	Intron 21 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.8233+1025C>G		intron_variant	Intron 22 of 44		NP_001415264.1
TNXB	NM_019105.8	c.7492+1025C>G		intron_variant	Intron 21 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.7492+1025C>G		intron_variant	Intron 21 of 43		NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.8233+1025C>G		intron_variant	Intron 22 of 44			ENSP00000497649.1
TNXB	ENST00000375244.7	c.7492+1025C>G		intron_variant	Intron 21 of 43	5		ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15035 AN: 146200 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0428

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0803

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

GnomAD4 genome AF: 0.103 AC: 15041 AN: 146312 Hom.: 980 Cov.: 32 AF XY: 0.0977 AC XY: 6954 AN XY: 71168

African (AFR) AF: 0.0586 AC: 2359 AN: 40282

American (AMR) AF: 0.0572 AC: 858 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 188 AN: 3376

East Asian (EAS) AF: 0.0202 AC: 94 AN: 4650

South Asian (SAS) AF: 0.0337 AC: 130 AN: 3862

European-Finnish (FIN) AF: 0.114 AC: 1162 AN: 10204

Middle Eastern (MID) AF: 0.0458 AC: 13 AN: 284

European-Non Finnish (NFE) AF: 0.152 AC: 9998 AN: 65716

Other (OTH) AF: 0.0795 AC: 163 AN: 2050

Alfa AF: 0.131 Hom.: 854

Bravo AF: 0.0924

Asia WGS AF: 0.0300 AC: 105 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.34
PhyloP100		0.96
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: rs1150758; hg19: chr6-32028149;