rs886038649

Variant names:

• chr6-32043421-C-T
• rs886038649
• NM_001365276.2:c.11650+16G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001365276.2(TNXB):​c.11650+16G>A 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 7)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.586
• 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: Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-32043421-C-T is Benign according to our data. Variant chr6-32043421-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 261116.Status of the report is criteria_provided_single_submitter, 1 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.11650+16G>A		intron	N/A	NP_001352205.1	P22105-3
	TNXB	NM_001428335.1		c.12391+16G>A		intron	N/A	NP_001415264.1	A0A3B3ISX9
	TNXB	NM_019105.8		c.11644+16G>A		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.11650+16G>A		intron	N/A	ENSP00000496448.1	P22105-3
	TNXB	ENST00000451343.4	TSL:1	c.937+16G>A		intron	N/A	ENSP00000407685.1	P22105-2
	TNXB	ENST00000490077.5	TSL:1	n.1477+16G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD2 exomes AF: 0.0000271 AC: 2 AN: 73844 AF XY: 0.0000528

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 13 AN: 474522 Hom.: 0 Cov.: 5 AF XY: 0.0000360 AC XY: 9 AN XY: 250204

African (AFR) AF: 0.00 AC: 0 AN: 13804

American (AMR) AF: 0.00 AC: 0 AN: 26654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15004

East Asian (EAS) AF: 0.00 AC: 0 AN: 31024

South Asian (SAS) AF: 0.000200 AC: 10 AN: 50020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2050

European-Non Finnish (NFE) AF: 0.0000107 AC: 3 AN: 279712

Other (OTH) AF: 0.00 AC: 0 AN: 26912

GnomAD4 genome Cov.: 7

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		-0.59

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886038649;

hg19: chr6-32011198;