chr6-32049328-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365276.2(TNXB):c.9699T>C(p.His3233His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,612,390 control chromosomes in the GnomAD database, including 3,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 286 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3114 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.996

Publications

7 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=-0.55).

BP6

Variant 6-32049328-A-G is Benign according to our data. Variant chr6-32049328-A-G is described in ClinVar as Benign. ClinVar VariationId is 261182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TNXB	NM_001365276.2	MANE Select	c.9699T>C	p.His3233His	synonymous	Exon 28 of 44	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.10440T>C	p.His3480His	synonymous	Exon 29 of 45	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.9693T>C	p.His3231His	synonymous	Exon 28 of 44	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.9699T>C	p.His3233His	synonymous	Exon 28 of 44	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1		c.10440T>C	p.His3480His	synonymous	Exon 29 of 45	ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7	TSL:5	c.9699T>C	p.His3233His	synonymous	Exon 28 of 44	ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7419

AN:

152058

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0991

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0440

GnomAD2 exomes

AF:

0.0581

AC:

14337

AN:

246932

AF XY:

0.0588

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0618

AC:

90172

AN:

1460214

Hom.:

3114

Cov.:

AF XY:

0.0613

AC XY:

44524

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.00951

AC:

318

AN:

33440

American (AMR)

AF:

0.0342

AC:

1528

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

450

AN:

26116

East Asian (EAS)

AF:

0.0777

AC:

3083

AN:

39698

South Asian (SAS)

AF:

0.0571

AC:

4925

AN:

86178

European-Finnish (FIN)

AF:

0.0624

AC:

3321

AN:

53256

Middle Eastern (MID)

AF:

0.0290

AC:

137

AN:

4730

European-Non Finnish (NFE)

AF:

0.0651

AC:

72362

AN:

1111830

Other (OTH)

AF:

0.0672

AC:

4048

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

7132

14264

21397

28529

35661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2658

5316

7974

10632

13290

<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:

0.0488

AC:

7432

AN:

152176

Hom.:

286

Cov.:

AF XY:

0.0490

AC XY:

3644

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0138

AC:

573

AN:

41536

American (AMR)

AF:

0.0345

AC:

527

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

AN:

3464

East Asian (EAS)

AF:

0.115

AC:

597

AN:

5172

South Asian (SAS)

AF:

0.0746

AC:

360

AN:

4824

European-Finnish (FIN)

AF:

0.0603

AC:

640

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0658

AC:

4473

AN:

67960

Other (OTH)

AF:

0.0502

AC:

106

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

375

749

1124

1498

1873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0548

Hom.:

135

Bravo

AF:

0.0439

Asia WGS

AF:

0.144

AC:

499

AN:

3478

EpiCase

AF:

0.0532

EpiControl

AF:

0.0582

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.9

(source)

DANN

Benign

0.29

PhyloP100

1.0

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

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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