chr6-32053353-C-T

Variant names:

• chr6-32053353-C-T
• rs11969759
• NM_001365276.2:c.8791+35G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365276.2(TNXB):​c.8791+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,598,890 control chromosomes in the GnomAD database, including 4,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (920 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3638 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.81
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-32053353-C-T is Benign according to our data. Variant chr6-32053353-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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.8791+35G>A		intron	N/A	NP_001352205.1
	TNXB	NM_001428335.1		c.9532+35G>A		intron	N/A	NP_001415264.1
	TNXB	NM_019105.8		c.8785+35G>A		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.8791+35G>A		intron	N/A	ENSP00000496448.1
	TNXB	ENST00000647633.1		c.9532+35G>A		intron	N/A	ENSP00000497649.1
	TNXB	ENST00000375244.7	TSL:5	c.8791+35G>A		intron	N/A	ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14885 AN: 152090 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0855

GnomAD2 exomes AF: 0.0783 AC: 17934 AN: 229070 AF XY: 0.0731

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.0919

Gnomad ASJ exome AF: 0.00991

Gnomad EAS exome AF: 0.0886

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.0626

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0642 AC: 92927 AN: 1446682 Hom.: 3638 Cov.: 33 AF XY: 0.0627 AC XY: 44998 AN XY: 717732

African (AFR) AF: 0.164 AC: 5429 AN: 33172

American (AMR) AF: 0.0844 AC: 3642 AN: 43142

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 280 AN: 25864

East Asian (EAS) AF: 0.0720 AC: 2828 AN: 39294

South Asian (SAS) AF: 0.0337 AC: 2865 AN: 84968

European-Finnish (FIN) AF: 0.159 AC: 8254 AN: 51750

Middle Eastern (MID) AF: 0.0461 AC: 214 AN: 4638

European-Non Finnish (NFE) AF: 0.0597 AC: 65902 AN: 1104088

Other (OTH) AF: 0.0588 AC: 3513 AN: 59766

GnomAD4 genome AF: 0.0978 AC: 14892 AN: 152208 Hom.: 920 Cov.: 32 AF XY: 0.100 AC XY: 7445 AN XY: 74408

African (AFR) AF: 0.162 AC: 6705 AN: 41494

American (AMR) AF: 0.0720 AC: 1102 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3466

East Asian (EAS) AF: 0.0825 AC: 427 AN: 5176

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1856 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4295 AN: 68010

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0699 Hom.: 528

Bravo AF: 0.0948

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.046
DANN	Benign	0.48
PhyloP100		-2.8
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: rs11969759; hg19: chr6-32021130;