dbSNP rs2395083: TNXB:c.11530+46C>T (chr6-32043703-G-A) – 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.11530+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,613,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 27)

Exomes 𝑓: 0.0036 ( 11 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.74

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=-0.9).

BP6

Variant 6-32043703-G-A is Benign according to our data. Variant chr6-32043703-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 261110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00362 (5283/1461056) while in subpopulation SAS AF = 0.0118 (1021/86228). AF 95% confidence interval is 0.0112. There are 11 homozygotes in GnomAdExome4. There are 2733 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 11 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.11530+46C>T	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12271+46C>T	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.11524+46C>T	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.11530+46C>T	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.817+46C>T	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1357+46C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

463

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00851

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00325

AC:

813

AN:

250172

AF XY:

0.00366

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00362

AC:

5283

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2733

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33480

American (AMR)

AF:

0.00168

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26134

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.0118

AC:

1021

AN:

86228

European-Finnish (FIN)

AF:

0.000683

AC:

AN:

52708

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00347

AC:

3857

AN:

1111932

Other (OTH)

AF:

0.00336

AC:

203

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

261

521

782

1042

1303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.00304

AC:

462

AN:

152070

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

208

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

41446

American (AMR)

AF:

0.00216

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5168

South Asian (SAS)

AF:

0.00831

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00363

AC:

247

AN:

67986

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00323

Hom.:

Bravo

AF:

0.00323

Asia WGS

AF:

0.00404

AC:

AN:

3478

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

-0.90

CADD

Benign

0.60

(source)

DANN

Benign

0.83

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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