chr6-32053067-G-A

Position:

• chr6-32053067-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365276.2(TNXB):​c.8792-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,499,794 control chromosomes in the GnomAD database, including 6,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (825 hom., cov: 31)
  • Exomes 𝑓: 0.086 (5698 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-32053067-G-A is Benign according to our data. Variant chr6-32053067-G-A is described in ClinVar as [Benign]. Clinvar id is 1263543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.8792-74C>T		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.8786-74C>T		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.8792-74C>T		intron_variant			NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.9533-74C>T		intron_variant				ENSP00000497649.1
TNXB	ENST00000375244.7	c.8792-74C>T		intron_variant		5		ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14785 AN: 152020 Hom.: 830 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0862 AC: 116188 AN: 1347656 Hom.: 5698 AF XY: 0.0870 AC XY: 58001 AN XY: 666622

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0206

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0533

Gnomad4 NFE exome AF: 0.0856

Gnomad4 OTH exome AF: 0.0922

GnomAD4 genome AF: 0.0972 AC: 14790 AN: 152138 Hom.: 825 Cov.: 31 AF XY: 0.0958 AC XY: 7122 AN XY: 74370

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0911 Hom.: 911

Bravo AF: 0.0994

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.37

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: rs2077580; hg19: chr6-32020844;