NM_001365276.2:c.-8-5034G>C

Variant names:

• chr6-32103240-C-G
• rs3117181
• NM_001365276.2:c.-8-5034G>C

Variant summary

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

The NM_001365276.2(TNXB):​c.-8-5034G>C 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 151,768 control chromosomes in the GnomAD database, including 62,227 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 (62227 hom., cov: 27)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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
TNXB	NM_001365276.2	c.-8-5034G>C		intron_variant	Intron 1 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.-8-5034G>C		intron_variant	Intron 1 of 44		NP_001415264.1
TNXB	NM_019105.8	c.-8-5034G>C		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.-8-5034G>C		intron_variant	Intron 1 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137116 AN: 151650 Hom.: 62163 Cov.: 27

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.889

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: 137239 AN: 151768 Hom.: 62227 Cov.: 27 AF XY: 0.905 AC XY: 67104 AN XY: 74140

African (AFR) AF: 0.970 AC: 40114 AN: 41370

American (AMR) AF: 0.924 AC: 14081 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3211 AN: 3466

East Asian (EAS) AF: 0.910 AC: 4673 AN: 5134

South Asian (SAS) AF: 0.914 AC: 4376 AN: 4786

European-Finnish (FIN) AF: 0.889 AC: 9378 AN: 10546

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

European-Non Finnish (NFE) AF: 0.859 AC: 58337 AN: 67918

Other (OTH) AF: 0.927 AC: 1947 AN: 2100

Alfa AF: 0.824 Hom.: 2505

Bravo AF: 0.911

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.37
PhyloP100		-1.4
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: rs3117181; hg19: chr6-32071017;