rs2395084

Variant names:

• chr6-32043712-G-A
• rs2395084
• NM_001365276.2:c.11530+37C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001365276.2(TNXB):​c.11530+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,613,286 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.457
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, PanelApp Australia
• familial vesicoureteral reflux

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-32043712-G-A is Benign according to our data. Variant chr6-32043712-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 261109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	NM_001365276.2	MANE Select	c.11530+37C>T		intron	N/A	NP_001352205.1	P22105-3
	TNXB	NM_001428335.1		c.12271+37C>T		intron	N/A	NP_001415264.1	A0A3B3ISX9
	TNXB	NM_019105.8		c.11524+37C>T		intron	N/A	NP_061978.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	ENST00000644971.2	MANE Select	c.11530+37C>T		intron	N/A	ENSP00000496448.1	P22105-3
	TNXB	ENST00000451343.4	TSL:1	c.817+37C>T		intron	N/A	ENSP00000407685.1	P22105-2
	TNXB	ENST00000490077.5	TSL:1	n.1357+37C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152022 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000316 AC: 79 AN: 250254 AF XY: 0.000339

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000434

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000479 AC: 700 AN: 1461146 Hom.: 1 Cov.: 32 AF XY: 0.000472 AC XY: 343 AN XY: 726898

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39700

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52726

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000531 AC: 591 AN: 1111966

Other (OTH) AF: 0.000447 AC: 27 AN: 60390

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152140 Hom.: 0 Cov.: 27 AF XY: 0.000323 AC XY: 24 AN XY: 74382

African (AFR) AF: 0.0000482 AC: 2 AN: 41486

American (AMR) AF: 0.000393 AC: 6 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67980

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000521 Hom.: 0

Bravo AF: 0.000400

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.94
DANN	Benign	0.76
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs2395084; hg19: chr6-32011489;