6-32044732-G-A

Variant names:

• chr6-32044732-G-A
• rs886038647
• NM_001365276.2:c.10928-16C>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.10928-16C>T 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: 𝑓 0.00044 (0 hom., cov: 7)
  • Exomes 𝑓: 0.00055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00400
• 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=-0.8).
• BP6: Variant 6-32044732-G-A is Benign according to our data. Variant chr6-32044732-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 261100.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.10928-16C>T		intron	N/A	NP_001352205.1	P22105-3
	TNXB	NM_001428335.1		c.11669-16C>T		intron	N/A	NP_001415264.1	A0A3B3ISX9
	TNXB	NM_019105.8		c.10922-16C>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.10928-16C>T		intron	N/A	ENSP00000496448.1	P22105-3
	TNXB	ENST00000451343.4	TSL:1	c.215-16C>T		intron	N/A	ENSP00000407685.1	P22105-2
	TNXB	ENST00000490077.5	TSL:1	n.755-16C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000436 AC: 24 AN: 55074 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.0000710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000677

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000477 AC: 26 AN: 54496 AF XY: 0.000437

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000787

Gnomad OTH exome AF: 0.000520

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000550 AC: 249 AN: 452506 Hom.: 0 Cov.: 0 AF XY: 0.000522 AC XY: 125 AN XY: 239268

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000791 AC: 1 AN: 12646

American (AMR) AF: 0.000983 AC: 20 AN: 20344

Ashkenazi Jewish (ASJ) AF: 0.00151 AC: 21 AN: 13924

East Asian (EAS) AF: 0.00 AC: 0 AN: 31100

South Asian (SAS) AF: 0.0000217 AC: 1 AN: 46022

European-Finnish (FIN) AF: 0.000206 AC: 6 AN: 29114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1992

European-Non Finnish (NFE) AF: 0.000701 AC: 190 AN: 271174

Other (OTH) AF: 0.000382 AC: 10 AN: 26190

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000435 AC: 24 AN: 55114 Hom.: 0 Cov.: 7 AF XY: 0.000414 AC XY: 10 AN XY: 24132

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000707 AC: 1 AN: 14154

American (AMR) AF: 0.000675 AC: 4 AN: 5922

Ashkenazi Jewish (ASJ) AF: 0.000581 AC: 1 AN: 1720

East Asian (EAS) AF: 0.00 AC: 0 AN: 2584

South Asian (SAS) AF: 0.00 AC: 0 AN: 1826

European-Finnish (FIN) AF: 0.000339 AC: 1 AN: 2954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.000692 AC: 17 AN: 24576

Other (OTH) AF: 0.00 AC: 0 AN: 786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.66
PhyloP100		-0.0040

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: rs886038647; hg19: chr6-32012509;