chr6-32078498-A-C

Position:

• chr6-32078498-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365276.2(TNXB):​c.4375+535T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,998 control chromosomes in the GnomAD database, including 915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.098 (911 hom., cov: 31)
  • Exomes 𝑓: 0.037 (4 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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]

RNA5SP206 (HGNC:43106): (RNA, 5S ribosomal pseudogene 206)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.4375+535T>G		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.4375+535T>G		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.4375+535T>G		intron_variant			NM_001365276.2	ENSP00000496448
TNXB	ENST00000375244.7	c.4375+535T>G		intron_variant		5		ENSP00000364393
TNXB	ENST00000647633.1	c.5116+535T>G		intron_variant				ENSP00000497649	P1
RNA5SP206	ENST00000516703.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14788 AN: 151140 Hom.: 909 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0851

GnomAD4 exome AF: 0.0370 AC: 65 AN: 1758 Hom.: 4 Cov.: 0 AF XY: 0.0410 AC XY: 41 AN XY: 1000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0139

Gnomad4 FIN exome AF: 0.0972

Gnomad4 NFE exome AF: 0.0348

Gnomad4 OTH exome AF: 0.0648

GnomAD4 genome AF: 0.0978 AC: 14796 AN: 151240 Hom.: 911 Cov.: 31 AF XY: 0.0999 AC XY: 7373 AN XY: 73812

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0728

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0641 Hom.: 711

Bravo AF: 0.0963

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.55

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: rs7774197; hg19: chr6-32046275;