rs2734313

Variant names:

• chr6-32043427-G-C
• rs2734313
• NM_001365276.2:c.11650+10C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32043427-G-C
• chr6-32043427-G-T

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.11650+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (4178 hom., cov: 7)
  • Exomes 𝑓: 0.45 (50170 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 4 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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-32043427-G-C is Benign according to our data. Variant chr6-32043427-G-C is described in ClinVar as Benign. ClinVar VariationId is 261115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.11650+10C>G		intron_variant	Intron 36 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.12391+10C>G		intron_variant	Intron 37 of 44		NP_001415264.1
TNXB	NM_019105.8	c.11644+10C>G		intron_variant	Intron 36 of 43		NP_061978.6
TNXB	NM_032470.4	c.937+10C>G		intron_variant	Intron 5 of 12		NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.11650+10C>G		intron_variant	Intron 36 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 17749 AN: 41826 Hom.: 4176 Cov.: 7

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.464 AC: 35360 AN: 76204 AF XY: 0.450

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.563

Gnomad EAS exome AF: 0.392

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.453 AC: 216796 AN: 478920 Hom.: 50170 Cov.: 5 AF XY: 0.450 AC XY: 113597 AN XY: 252172

African (AFR) AF: 0.466 AC: 6497 AN: 13956

American (AMR) AF: 0.575 AC: 15842 AN: 27568

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 8624 AN: 15104

East Asian (EAS) AF: 0.445 AC: 13725 AN: 30858

South Asian (SAS) AF: 0.402 AC: 20164 AN: 50146

European-Finnish (FIN) AF: 0.445 AC: 13058 AN: 29336

Middle Eastern (MID) AF: 0.496 AC: 1016 AN: 2050

European-Non Finnish (NFE) AF: 0.444 AC: 125685 AN: 282776

Other (OTH) AF: 0.449 AC: 12185 AN: 27126

GnomAD4 genome AF: 0.424 AC: 17758 AN: 41862 Hom.: 4178 Cov.: 7 AF XY: 0.425 AC XY: 7617 AN XY: 17932

African (AFR) AF: 0.430 AC: 3983 AN: 9272

American (AMR) AF: 0.489 AC: 2003 AN: 4100

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 637 AN: 1182

East Asian (EAS) AF: 0.382 AC: 758 AN: 1984

South Asian (SAS) AF: 0.396 AC: 566 AN: 1428

European-Finnish (FIN) AF: 0.434 AC: 1114 AN: 2568

Middle Eastern (MID) AF: 0.414 AC: 72 AN: 174

European-Non Finnish (NFE) AF: 0.405 AC: 8259 AN: 20394

Other (OTH) AF: 0.445 AC: 242 AN: 544

Alfa AF: 0.445 Hom.: 1916

Bravo AF: 0.466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 10, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2734313; hg19: chr6-32011204;