rs17421624

Positions:

• chr6-32098400-T-C
• chr6-32098400-T-G

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.-8-194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,108 control chromosomes in the GnomAD database, including 6,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (6055 hom., cov: 32)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0800

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-32098400-T-C is Benign according to our data. Variant chr6-32098400-T-C is described in ClinVar as [Benign]. Clinvar id is 1272407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.-8-194A>G		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.-8-194A>G		intron_variant			NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.-8-194A>G		intron_variant			NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37860 AN: 151990 Hom.: 6048 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37874 AN: 152108 Hom.: 6055 Cov.: 32 AF XY: 0.256 AC XY: 19013 AN XY: 74372

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.240

Alfa AF: 0.310 Hom.: 7278

Bravo AF: 0.240

Asia WGS AF: 0.221 AC: 770 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	-0.78
CADD	Benign	8.8
DANN	Benign	0.82

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: rs17421624; hg19: chr6-32066177;