rs204883
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001365276.2(TNXB):c.6696C>T(p.Asp2232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,612,086 control chromosomes in the GnomAD database, including 133,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.38 ( 11883 hom., cov: 31)
Exomes 𝑓: 0.40 ( 122050 hom. )
Consequence
TNXB
NM_001365276.2 synonymous
NM_001365276.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.29
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 6-32064966-G-A is Benign according to our data. Variant chr6-32064966-G-A is described in ClinVar as [Benign]. Clinvar id is 261150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32064966-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.28 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.6696C>T | p.Asp2232= | synonymous_variant | 19/44 | ENST00000644971.2 | |
TNXB | NM_019105.8 | c.6696C>T | p.Asp2232= | synonymous_variant | 19/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNXB | ENST00000644971.2 | c.6696C>T | p.Asp2232= | synonymous_variant | 19/44 | NM_001365276.2 | |||
TNXB | ENST00000647633.1 | c.7437C>T | p.Asp2479= | synonymous_variant | 20/45 | P1 | |||
TNXB | ENST00000375244.7 | c.6696C>T | p.Asp2232= | synonymous_variant | 19/44 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.381 AC: 57919AN: 151920Hom.: 11874 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
57919
AN:
151920
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.438 AC: 106625AN: 243534Hom.: 24451 AF XY: 0.435 AC XY: 58028AN XY: 133270
GnomAD3 exomes
AF:
AC:
106625
AN:
243534
Hom.:
AF XY:
AC XY:
58028
AN XY:
133270
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.404 AC: 589342AN: 1460048Hom.: 122050 Cov.: 69 AF XY: 0.405 AC XY: 294009AN XY: 726294
GnomAD4 exome
AF:
AC:
589342
AN:
1460048
Hom.:
Cov.:
69
AF XY:
AC XY:
294009
AN XY:
726294
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.381 AC: 57948AN: 152038Hom.: 11883 Cov.: 31 AF XY: 0.387 AC XY: 28749AN XY: 74314
GnomAD4 genome
?
AF:
AC:
57948
AN:
152038
Hom.:
Cov.:
31
AF XY:
AC XY:
28749
AN XY:
74314
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1323
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Vesicoureteral reflux 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Ehlers-Danlos syndrome due to tenascin-X deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 04, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at