Genetic Variant NM_001365276.2:c.8601C>T (chr6-32053578-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001365276.2(TNXB):c.8601C>T(p.Pro2867Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,613,638 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 79 hom. )

Consequence

TNXB
NM_001365276.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.39

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 6-32053578-G-A is Benign according to our data. Variant chr6-32053578-G-A is described in ClinVar as Benign. ClinVar VariationId is 261170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0086 (1309/152262) while in subpopulation NFE AF = 0.0122 (830/68018). AF 95% confidence interval is 0.0115. There are 5 homozygotes in GnomAd4. There are 658 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 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	HGVSp	Effect	Exon Rank	Protein	UniProt
TNXB	NM_001365276.2	MANE Select	c.8601C>T	p.Pro2867Pro	synonymous	Exon 25 of 44	NP_001352205.1	P22105-3
TNXB	NM_001428335.1		c.9342C>T	p.Pro3114Pro	synonymous	Exon 26 of 45	NP_001415264.1	A0A3B3ISX9
TNXB	NM_019105.8		c.8595C>T	p.Pro2865Pro	synonymous	Exon 25 of 44	NP_061978.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNXB	ENST00000644971.2	MANE Select	c.8601C>T	p.Pro2867Pro	synonymous	Exon 25 of 44	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1		c.9342C>T	p.Pro3114Pro	synonymous	Exon 26 of 45	ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7	TSL:5	c.8601C>T	p.Pro2867Pro	synonymous	Exon 25 of 44	ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1311

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00961

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00859

AC:

2121

AN:

246948

AF XY:

0.00902

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00568

Gnomad ASJ exome

AF:

0.00590

Gnomad EAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.00995

AC:

14535

AN:

1461376

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7335

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33474

American (AMR)

AF:

0.00577

AC:

258

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00673

AC:

176

AN:

26136

East Asian (EAS)

AF:

0.000479

AC:

AN:

39700

South Asian (SAS)

AF:

0.00812

AC:

700

AN:

86254

European-Finnish (FIN)

AF:

0.0118

AC:

627

AN:

53192

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0110

AC:

12201

AN:

1111844

Other (OTH)

AF:

0.00827

AC:

499

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1207

2414

3622

4829

6036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.00860

AC:

1309

AN:

152262

Hom.:

Cov.:

AF XY:

0.00884

AC XY:

658

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

41546

American (AMR)

AF:

0.0118

AC:

181

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3468

East Asian (EAS)

AF:

0.00194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0101

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00961

AC:

102

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

830

AN:

68018

Other (OTH)

AF:

0.00664

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

135

202

270

337

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:

0.0105

Hom.:

Bravo

AF:

0.00811

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00895

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cardiovascular phenotype (1)

Ehlers-Danlos syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.47

(source)

DANN

Benign

0.52

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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