dbSNP rs77466839: TNXB:c.11264-20G>A (chr6-32044149-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365276.2(TNXB):c.11264-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,471,384 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 19)

Exomes 𝑓: 0.019 ( 492 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.64

Publications

0 publications found

Variant links:

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)

TNXB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-32044149-C-T is Benign according to our data. Variant chr6-32044149-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 261104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0162 (2150/132592) while in subpopulation NFE AF = 0.0235 (1443/61452). AF 95% confidence interval is 0.0225. There are 56 homozygotes in GnomAd4. There are 1059 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 56 AR,AD gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	NM_001365276.2	MANE Select	c.11264-20G>A	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12005-20G>A	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.11258-20G>A	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.11264-20G>A	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.551-20G>A	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1091-20G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2155

AN:

132510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00318

Gnomad AMI

AF:

0.0151

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.0194

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.0304

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0185

AC:

3726

AN:

201420

AF XY:

0.0187

show subpopulations

Gnomad AFR exome

AF:

0.00287

Gnomad AMR exome

AF:

0.00922

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.0216

Gnomad FIN exome

AF:

0.0295

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0192

AC:

25760

AN:

1338792

Hom.:

492

Cov.:

AF XY:

0.0192

AC XY:

12779

AN XY:

665472

show subpopulations

African (AFR)

AF:

0.00261

AC:

AN:

30612

American (AMR)

AF:

0.00919

AC:

363

AN:

39516

Ashkenazi Jewish (ASJ)

AF:

0.0197

AC:

492

AN:

24928

East Asian (EAS)

AF:

0.0123

AC:

461

AN:

37624

South Asian (SAS)

AF:

0.0147

AC:

1142

AN:

77604

European-Finnish (FIN)

AF:

0.0288

AC:

1397

AN:

48426

Middle Eastern (MID)

AF:

0.0209

AC:

AN:

4162

European-Non Finnish (NFE)

AF:

0.0204

AC:

20787

AN:

1020046

Other (OTH)

AF:

0.0170

AC:

951

AN:

55874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

764

1527

2291

3054

3818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0162

AC:

2150

AN:

132592

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1059

AN XY:

64068

show subpopulations

African (AFR)

AF:

0.00317

AC:

109

AN:

34388

American (AMR)

AF:

0.00529

AC:

AN:

13230

Ashkenazi Jewish (ASJ)

AF:

0.0194

AC:

AN:

3204

East Asian (EAS)

AF:

0.0195

AC:

AN:

4554

South Asian (SAS)

AF:

0.0130

AC:

AN:

3856

European-Finnish (FIN)

AF:

0.0315

AC:

284

AN:

9026

Middle Eastern (MID)

AF:

0.0219

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0235

AC:

1443

AN:

61452

Other (OTH)

AF:

0.0138

AC:

AN:

1814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0141

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.020

(source)

DANN

Benign

0.56

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over