6-32107786-T-C

Variant names:

• chr6-32107786-T-C
• rs429150
• NM_001365276.2:c.-9+1395A>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.-9+1395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,772 control chromosomes in the GnomAD database, including 18,824 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 0.49 (18824 hom., cov: 30)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 34 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)

ENSG00000284829 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	NM_001365276.2	MANE Select	c.-9+1395A>G		intron	N/A	NP_001352205.1
	TNXB	NM_001428335.1		c.-9+1395A>G		intron	N/A	NP_001415264.1
	TNXB	NM_019105.8		c.-9+1395A>G		intron	N/A	NP_061978.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	ENST00000644971.2	MANE Select	c.-9+1395A>G		intron	N/A	ENSP00000496448.1
	TNXB	ENST00000479795.1	TSL:1	c.-9+1395A>G		intron	N/A	ENSP00000418248.1
	TNXB	ENST00000442721.1	TSL:1	c.-9+7208A>G		intron	N/A	ENSP00000389946.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74830 AN: 151654 Hom.: 18824 Cov.: 30

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.493 AC: 74875 AN: 151772 Hom.: 18824 Cov.: 30 AF XY: 0.502 AC XY: 37223 AN XY: 74162

African (AFR) AF: 0.452 AC: 18711 AN: 41360

American (AMR) AF: 0.493 AC: 7515 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2254 AN: 3462

East Asian (EAS) AF: 0.521 AC: 2683 AN: 5152

South Asian (SAS) AF: 0.661 AC: 3172 AN: 4798

European-Finnish (FIN) AF: 0.553 AC: 5818 AN: 10526

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32864 AN: 67918

Other (OTH) AF: 0.519 AC: 1091 AN: 2104

Alfa AF: 0.459 Hom.: 11809

Bravo AF: 0.486

Asia WGS AF: 0.590 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-0.051
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: rs429150; hg19: chr6-32075563;