rs3130342

Variant names:

• chr6-32112369-A-C
• rs3130342
• ENST00000442721.1:c.-9+2625T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32112369-A-C
• chr6-32112369-A-G
• chr6-32112369-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000442721.1(TNXB):​c.-9+2625T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,120 control chromosomes in the GnomAD database, including 62,361 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 0.90 (62361 hom., cov: 30)
• Consequence: TNXB ENST00000442721.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 56 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)

ENSG00000286974 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000442721.1	c.-9+2625T>G		intron_variant	Intron 1 of 1	1		ENSP00000389946.1
ENSG00000286974	ENST00000656765.1	n.2005A>C		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000284829	ENST00000494022.1	n.289+4335T>G		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137422 AN: 152002 Hom.: 62297 Cov.: 30

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.904 AC: 137545 AN: 152120 Hom.: 62361 Cov.: 30 AF XY: 0.905 AC XY: 67310 AN XY: 74360

African (AFR) AF: 0.970 AC: 40245 AN: 41496

American (AMR) AF: 0.923 AC: 14095 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3213 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4688 AN: 5162

South Asian (SAS) AF: 0.914 AC: 4401 AN: 4816

European-Finnish (FIN) AF: 0.890 AC: 9419 AN: 10588

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58409 AN: 67998

Other (OTH) AF: 0.927 AC: 1956 AN: 2110

Alfa AF: 0.880 Hom.: 223456

Bravo AF: 0.911

Asia WGS AF: 0.937 AC: 3258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3130342; hg19: chr6-32080146;