rs12153855

Variant names:

• chr6-32107027-T-C
• rs12153855
• NM_001365276.2:c.-9+2154A>G

Variant summary

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

The NM_001365276.2(TNXB):​c.-9+2154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,284 control chromosomes in the GnomAD database, including 1,083 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 0.11 (1083 hom., cov: 32)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 80 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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.-9+2154A>G		intron_variant	Intron 1 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.-9+2154A>G		intron_variant	Intron 1 of 44		NP_001415264.1
TNXB	NM_019105.8	c.-9+2154A>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.-9+2154A>G		intron_variant	Intron 1 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17238 AN: 152166 Hom.: 1088 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.113 AC: 17236 AN: 152284 Hom.: 1083 Cov.: 32 AF XY: 0.111 AC XY: 8257 AN XY: 74464

African (AFR) AF: 0.155 AC: 6435 AN: 41544

American (AMR) AF: 0.0800 AC: 1224 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.0393 AC: 204 AN: 5186

South Asian (SAS) AF: 0.156 AC: 752 AN: 4828

European-Finnish (FIN) AF: 0.0558 AC: 593 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7172 AN: 68006

Other (OTH) AF: 0.112 AC: 237 AN: 2116

Alfa AF: 0.103 Hom.: 3590

Bravo AF: 0.118

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		0.29
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: rs12153855; hg19: chr6-32074804;