dbSNP rs562705617: TNXB:c.12058+11G>A (chr6-32042688-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.12058+11G>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: 𝑓 0.011 ( 13 hom., cov: 15)

Exomes 𝑓: 0.016 ( 211 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.73

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: 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)

TNXB links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001365276.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 6-32042688-C-T is Benign according to our data. Variant chr6-32042688-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 261118.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 = 0.0113 (1332/117466) while in subpopulation NFE AF = 0.0182 (1012/55542). AF 95% confidence interval is 0.0173. There are 13 homozygotes in GnomAd4. There are 608 alleles in the male GnomAd4 subpopulation. Median coverage is 15. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 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.12058+11G>A	intron	N/A	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.12799+11G>A	intron	N/A	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.12052+11G>A	intron	N/A	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.12058+11G>A	intron	N/A	ENSP00000496448.1	P22105-3
TNXB	ENST00000451343.4	TSL:1	c.1345+11G>A	intron	N/A	ENSP00000407685.1	P22105-2
TNXB	ENST00000490077.5	TSL:1	n.1885+11G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1332

AN:

117350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00174

Gnomad ASJ

AF:

0.00101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000314

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.00484

GnomAD2 exomes

AF:

0.0102

AC:

1351

AN:

133078

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.000752

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.00641

GnomAD4 exome

AF:

0.0159

AC:

17226

AN:

1086778

Hom.:

211

Cov.:

AF XY:

0.0153

AC XY:

8365

AN XY:

546304

show subpopulations

African (AFR)

AF:

0.00216

AC:

AN:

26902

American (AMR)

AF:

0.00160

AC:

AN:

35068

Ashkenazi Jewish (ASJ)

AF:

0.000908

AC:

AN:

23116

East Asian (EAS)

AF:

0.00

AC:

AN:

33846

South Asian (SAS)

AF:

0.0000402

AC:

AN:

74704

European-Finnish (FIN)

AF:

0.0316

AC:

1144

AN:

36160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3570

European-Non Finnish (NFE)

AF:

0.0192

AC:

15465

AN:

805444

Other (OTH)

AF:

0.00999

AC:

479

AN:

47968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

796

1592

2387

3183

3979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.0113

AC:

1332

AN:

117466

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

608

AN XY:

56140

show subpopulations

African (AFR)

AF:

0.00269

AC:

AN:

29744

American (AMR)

AF:

0.00174

AC:

AN:

12084

Ashkenazi Jewish (ASJ)

AF:

0.00101

AC:

AN:

2968

East Asian (EAS)

AF:

0.00

AC:

AN:

3682

South Asian (SAS)

AF:

0.000314

AC:

AN:

3180

European-Finnish (FIN)

AF:

0.0263

AC:

208

AN:

7896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0182

AC:

1012

AN:

55542

Other (OTH)

AF:

0.00476

AC:

AN:

1470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00658

Hom.:

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

-0.92

CADD

Benign

0.077

(source)

DANN

Benign

0.80

PhyloP100

-2.7

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

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

Publications

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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