rs41316640

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.12210+43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,428,772 control chromosomes in the GnomAD database, including 869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 20)

Exomes 𝑓: 0.0013 ( 869 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.618

Publications

1 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: 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)

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=-0.92).

BP6

Variant 6-32042412-A-C is Benign according to our data. Variant chr6-32042412-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 261122.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 = 0.00125 (1786/1428772) while in subpopulation SAS AF = 0.0099 (800/80790). AF 95% confidence interval is 0.00933. There are 869 homozygotes in GnomAdExome4. There are 1152 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 869 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.12210+43T>G	intron_variant	Intron 40 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.12951+43T>G	intron_variant	Intron 41 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.12204+43T>G	intron_variant	Intron 40 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 link	c.1497+43T>G	intron_variant	Intron 9 of 12		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.12210+43T>G		intron_variant	Intron 40 of 43		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.000800

AC:

110

AN:

137566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

Gnomad ASJ

AF:

0.000307

Gnomad EAS

AF:

0.000616

Gnomad SAS

AF:

0.000715

Gnomad FIN

AF:

0.0000984

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000439

Gnomad OTH

AF:

0.00106

GnomAD2 exomes

AF:

0.0000890

AC:

AN:

247112

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.00125

AC:

1786

AN:

1428772

Hom.:

869

Cov.:

AF XY:

0.00162

AC XY:

1152

AN XY:

709880

show subpopulations

African (AFR)

AF:

0.00527

AC:

163

AN:

30954

American (AMR)

AF:

0.00124

AC:

AN:

44192

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

25518

East Asian (EAS)

AF:

0.000462

AC:

AN:

38932

South Asian (SAS)

AF:

0.00990

AC:

800

AN:

80790

European-Finnish (FIN)

AF:

0.000305

AC:

AN:

52448

Middle Eastern (MID)

AF:

0.00177

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.000571

AC:

623

AN:

1091370

Other (OTH)

AF:

0.00100

AC:

AN:

58930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000828

AC:

114

AN:

137684

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

AN XY:

67192

show subpopulations

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

African (AFR)

AF:

0.00212

AC:

AN:

33960

American (AMR)

AF:

0.000277

AC:

AN:

14460

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

3260

East Asian (EAS)

AF:

0.000618

AC:

AN:

4858

South Asian (SAS)

AF:

0.000715

AC:

AN:

4194

European-Finnish (FIN)

AF:

0.0000984

AC:

AN:

10164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000439

AC:

AN:

63766

Other (OTH)

AF:

0.00104

AC:

AN:

1914

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.245

Heterozygous variant carriers

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:

0.00198

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.9

(source)

DANN

Benign

0.46

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over