Genetic Variant NM_001365276.2:c.7797G>A (chr6-32058086-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365276.2(TNXB):c.7797G>A(p.Leu2599Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,610,946 control chromosomes in the GnomAD database, including 17,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 937 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16286 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.21

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-32058086-C-T is Benign according to our data. Variant chr6-32058086-C-T is described in ClinVar as Benign. ClinVar VariationId is 261165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 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.7797G>A	p.Leu2599Leu	synonymous	Exon 22 of 44	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.8538G>A	p.Leu2846Leu	synonymous	Exon 23 of 45	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.7797G>A	p.Leu2599Leu	synonymous	Exon 22 of 44	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.7797G>A	p.Leu2599Leu	synonymous	Exon 22 of 44	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1		c.8538G>A	p.Leu2846Leu	synonymous	Exon 23 of 45	ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7	TSL:5	c.7797G>A	p.Leu2599Leu	synonymous	Exon 22 of 44	ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0989

AC:

15040

AN:

152140

Hom.:

935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0559

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.0780

GnomAD2 exomes

AF:

0.0908

AC:

22249

AN:

244988

AF XY:

0.0898

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.0531

Gnomad EAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.0918

GnomAD4 exome

AF:

0.139

AC:

202166

AN:

1458688

Hom.:

16286

Cov.:

AF XY:

0.135

AC XY:

97956

AN XY:

725390

show subpopulations

African (AFR)

AF:

0.0577

AC:

1929

AN:

33432

American (AMR)

AF:

0.0433

AC:

1930

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

1505

AN:

26062

East Asian (EAS)

AF:

0.0185

AC:

735

AN:

39640

South Asian (SAS)

AF:

0.0268

AC:

2308

AN:

86176

European-Finnish (FIN)

AF:

0.115

AC:

5990

AN:

52268

Middle Eastern (MID)

AF:

0.0304

AC:

173

AN:

5684

European-Non Finnish (NFE)

AF:

0.162

AC:

180357

AN:

1110592

Other (OTH)

AF:

0.120

AC:

7239

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11056

22112

33167

44223

55279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6384

12768

19152

25536

31920

<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:

0.0988

AC:

15046

AN:

152258

Hom.:

937

Cov.:

AF XY:

0.0935

AC XY:

6961

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0558

AC:

2321

AN:

41560

American (AMR)

AF:

0.0561

AC:

859

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3468

East Asian (EAS)

AF:

0.0184

AC:

AN:

5172

South Asian (SAS)

AF:

0.0273

AC:

132

AN:

4832

European-Finnish (FIN)

AF:

0.110

AC:

1173

AN:

10620

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

10026

AN:

67982

Other (OTH)

AF:

0.0772

AC:

163

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

715

1429

2144

2858

3573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.123

Hom.:

570

Bravo

AF:

0.0917

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.124

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.5

(source)

DANN

Benign

0.55

PhyloP100

-1.2

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