rs11969759

Positions:

• chr6-32053353-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.8791+35G>A		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.8785+35G>A		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.8791+35G>A		intron_variant			NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.9532+35G>A		intron_variant				ENSP00000497649.1
TNXB	ENST00000375244.7	c.8791+35G>A		intron_variant		5		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

GnomAD3 exomes AF: 0.0783 AC: 17934 AN: 229070 Hom.: 947 AF XY: 0.0731 AC XY: 9170 AN XY: 125480

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 SAS exome AF: 0.0326

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

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0844

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.0588

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

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0720

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.0632

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0625 Hom.: 242

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.046
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs11969759; hg19: chr6-32021130;