rs886038647

Positions:

• chr6-32044732-G-A
• chr6-32044732-G-C
• chr6-32044732-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001365276.2(TNXB):​c.10928-16C>T variant causes a splice polypyrimidine tract, 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 0.00044 (0 hom., cov: 7)
  • Exomes 𝑓: 0.00055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-32044732-G-A is Benign according to our data. Variant chr6-32044732-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261100.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32044732-G-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.10928-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000644971.2
TNXB	NM_019105.8	c.10922-16C>T		splice_polypyrimidine_tract_variant, intron_variant
TNXB	NM_032470.4	c.215-16C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.10928-16C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001365276.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 24 AN: 55074 Hom.: 0 Cov.: 7 FAILED QC

Gnomad AFR AF: 0.0000710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000677

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000477 AC: 26 AN: 54496 Hom.: 0 AF XY: 0.000437 AC XY: 12 AN XY: 27482

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000787

Gnomad OTH exome AF: 0.000520

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000550 AC: 249 AN: 452506 Hom.: 0 Cov.: 0 AF XY: 0.000522 AC XY: 125 AN XY: 239268

Gnomad4 AFR exome AF: 0.0000791

Gnomad4 AMR exome AF: 0.000983

Gnomad4 ASJ exome AF: 0.00151

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000217

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000701

Gnomad4 OTH exome AF: 0.000382

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000435 AC: 24 AN: 55114 Hom.: 0 Cov.: 7 AF XY: 0.000414 AC XY: 10 AN XY: 24132

Gnomad4 AFR AF: 0.0000707

Gnomad4 AMR AF: 0.000675

Gnomad4 ASJ AF: 0.000581

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000339

Gnomad4 NFE AF: 0.000692

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.80
CADD	Benign	7.4
DANN	Benign	0.66

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: rs886038647; hg19: chr6-32012509;