6-32103061-T-C

Variant names:

• chr6-32103061-T-C
• rs1269854
• NM_001365276.2:c.-8-4855A>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.-8-4855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 152,238 control chromosomes in the GnomAD database, including 343 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 0.056 (343 hom., cov: 32)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.-8-4855A>G		intron	N/A	NP_001352205.1
	TNXB	NM_001428335.1		c.-8-4855A>G		intron	N/A	NP_001415264.1
	TNXB	NM_019105.8		c.-8-4855A>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.-8-4855A>G		intron	N/A	ENSP00000496448.1
	TNXB	ENST00000479795.1	TSL:1	c.-8-4855A>G		intron	N/A	ENSP00000418248.1
	TNXB	ENST00000442721.1	TSL:1	c.-8-4855A>G		intron	N/A	ENSP00000389946.1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8525 AN: 152120 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0561 AC: 8539 AN: 152238 Hom.: 343 Cov.: 32 AF XY: 0.0526 AC XY: 3916 AN XY: 74450

African (AFR) AF: 0.105 AC: 4360 AN: 41512

American (AMR) AF: 0.0593 AC: 906 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2968 AN: 68012

Other (OTH) AF: 0.0578 AC: 122 AN: 2112

Alfa AF: 0.0444 Hom.: 735

Bravo AF: 0.0644

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.29
PhyloP100		-0.58
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: rs1269854; hg19: chr6-32070838;