rs17421624

Variant names:

• chr6-32098400-T-C
• rs17421624
• NM_001365276.2:c.-8-194A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome due to tenascin-X deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina, PanelApp Australia, Orphanet
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• vesicoureteral reflux 8

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000284829 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.-8-194A>G		intron_variant	Intron 1 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.-8-194A>G		intron_variant	Intron 1 of 44		NP_001415264.1
TNXB	NM_019105.8	c.-8-194A>G		intron_variant	Intron 1 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.-8-194A>G		intron_variant	Intron 1 of 43		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

African (AFR) AF: 0.0576 AC: 2391 AN: 41534

American (AMR) AF: 0.368 AC: 5620 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1546 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5176

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4222 AN: 10556

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20915 AN: 67962

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.294 Hom.: 19700

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

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	-0.78
CADD	Benign	8.8
DANN	Benign	0.82
PhyloP100		0.080
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17421624; hg19: chr6-32066177;