6-32044177-T-C

Position:

• chr6-32044177-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001365276.2(TNXB):​c.11264-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (656 hom., cov: 18)
  • Exomes 𝑓: 0.093 (23017 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.07

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 6-32044177-T-C is Benign according to our data. Variant chr6-32044177-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32044177-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.11264-48A>G		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.11258-48A>G		intron_variant			NP_061978.6
TNXB	NM_032470.4	c.551-48A>G		intron_variant			NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.11264-48A>G		intron_variant			NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10082 AN: 91794 Hom.: 654 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.0935

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0920

GnomAD3 exomes AF: 0.0151 AC: 2728 AN: 180354 Hom.: 608 AF XY: 0.0147 AC XY: 1436 AN XY: 97496

Gnomad AFR exome AF: 0.00468

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.0585

Gnomad SAS exome AF: 0.0435

Gnomad FIN exome AF: 0.00625

Gnomad NFE exome AF: 0.00577

Gnomad OTH exome AF: 0.0162

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0931 AC: 99289 AN: 1066198 Hom.: 23017 Cov.: 31 AF XY: 0.0984 AC XY: 52088 AN XY: 529618

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.110 AC: 10085 AN: 91830 Hom.: 656 Cov.: 18 AF XY: 0.108 AC XY: 4792 AN XY: 44482

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0955

Alfa AF: 0.0601 Hom.: 209

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.9
DANN	Benign	0.35

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: rs2856450; hg19: chr6-32011954;