chr6-32045040-C-T

Variant names:

• chr6-32045040-C-T
• rs113926083
• NM_001365276.2:c.10893G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001365276.2(TNXB):​c.10893G>A​(p.Lys3631Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 148,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (0 hom., cov: 25)
  • Exomes 𝑓: 0.068 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.747

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-32045040-C-T is Benign according to our data. Variant chr6-32045040-C-T is described in ClinVar as [Benign]. Clinvar id is 261099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.747 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.10893G>A	p.Lys3631Lys	synonymous_variant	Exon 32 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.11634G>A	p.Lys3878Lys	synonymous_variant	Exon 33 of 45		NP_001415264.1
TNXB	NM_019105.8	c.10887G>A	p.Lys3629Lys	synonymous_variant	Exon 32 of 44		NP_061978.6
TNXB	NM_032470.4	c.180G>A	p.Lys60Lys	synonymous_variant	Exon 1 of 13		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.10893G>A	p.Lys3631Lys	synonymous_variant	Exon 32 of 44		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7308 AN: 148344 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00468

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0946

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.0517

GnomAD3 exomes AF: 0.0526 AC: 12016 AN: 228440 Hom.: 1 AF XY: 0.0539 AC XY: 6735 AN XY: 124934

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0316

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.00660

Gnomad SAS exome AF: 0.0264

Gnomad FIN exome AF: 0.0369

Gnomad NFE exome AF: 0.0770

Gnomad OTH exome AF: 0.0650

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0683 AC: 95093 AN: 1391566 Hom.: 3 Cov.: 33 AF XY: 0.0681 AC XY: 47162 AN XY: 693038

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.00997

Gnomad4 SAS exome AF: 0.0263

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0770

Gnomad4 OTH exome AF: 0.0681

GnomAD4 genome AF: 0.0492 AC: 7307 AN: 148460 Hom.: 0 Cov.: 25 AF XY: 0.0470 AC XY: 3412 AN XY: 72642

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00469

Gnomad4 SAS AF: 0.0231

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0763

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0830 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.4
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113926083; hg19: chr6-32012817; COSMIC: COSV64472793; COSMIC: COSV64472793;