rs369637
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001365276.2(TNXB):c.7797G>A(p.Leu2599=) 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
NM_001365276.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.21
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id is 261165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32058086-C-T is described in Lovd as [Benign].
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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.7797G>A | p.Leu2599= | synonymous_variant | 22/44 | ENST00000644971.2 | |
TNXB | NM_019105.8 | c.7797G>A | p.Leu2599= | synonymous_variant | 22/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNXB | ENST00000644971.2 | c.7797G>A | p.Leu2599= | synonymous_variant | 22/44 | NM_001365276.2 | |||
TNXB | ENST00000647633.1 | c.8538G>A | p.Leu2846= | synonymous_variant | 23/45 | P1 | |||
TNXB | ENST00000375244.7 | c.7797G>A | p.Leu2599= | synonymous_variant | 22/44 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0989 AC: 15040AN: 152140Hom.: 935 Cov.: 32
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GnomAD3 exomes AF: 0.0908 AC: 22249AN: 244988Hom.: 1419 AF XY: 0.0898 AC XY: 11996AN XY: 133562
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GnomAD4 exome AF: 0.139 AC: 202166AN: 1458688Hom.: 16286 Cov.: 31 AF XY: 0.135 AC XY: 97956AN XY: 725390
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GnomAD4 genome ? AF: 0.0988 AC: 15046AN: 152258Hom.: 937 Cov.: 32 AF XY: 0.0935 AC XY: 6961AN XY: 74444
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ClinVar
Significance: Benign
Submissions summary: Benign:3
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 | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2018 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at