chr6-32043592-G-A

Variant names:

• chr6-32043592-G-A
• rs71565305
• NM_001365276.2:c.11531-36C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365276.2(TNXB):​c.11531-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,199,280 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.11531-36C>T		intron_variant	Intron 35 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.12272-36C>T		intron_variant	Intron 36 of 44		NP_001415264.1
TNXB	NM_019105.8	c.11525-36C>T		intron_variant	Intron 35 of 43		NP_061978.6
TNXB	NM_032470.4	c.818-36C>T		intron_variant	Intron 4 of 12		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.11531-36C>T		intron_variant	Intron 35 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.0000141 AC: 2 AN: 141546 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000662 AC: 7 AN: 1057734 Hom.: 0 Cov.: 14 AF XY: 0.00000738 AC XY: 4 AN XY: 542326

African (AFR) AF: 0.0000396 AC: 1 AN: 25234

American (AMR) AF: 0.00 AC: 0 AN: 44164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23578

East Asian (EAS) AF: 0.00 AC: 0 AN: 37788

South Asian (SAS) AF: 0.00 AC: 0 AN: 77834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3704

European-Non Finnish (NFE) AF: 0.00000659 AC: 5 AN: 759022

Other (OTH) AF: 0.0000211 AC: 1 AN: 47336

GnomAD4 genome AF: 0.0000141 AC: 2 AN: 141546 Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 2 AN XY: 68410

African (AFR) AF: 0.0000271 AC: 1 AN: 36848

American (AMR) AF: 0.0000701 AC: 1 AN: 14272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4644

South Asian (SAS) AF: 0.00 AC: 0 AN: 4148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65306

Other (OTH) AF: 0.00 AC: 0 AN: 1872

Alfa AF: 0.00 Hom.: 99

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.94
PhyloP100		-0.90

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: rs71565305; hg19: chr6-32011369;