rs204885
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1
The NM_001365276.2(TNXB):c.7168+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.0364 in 1,609,336 control chromosomes in the GnomAD database, including 1,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.043 ( 189 hom., cov: 32)
Exomes 𝑓: 0.036 ( 1150 hom. )
Consequence
TNXB
NM_001365276.2 splice_donor_5th_base, intron
NM_001365276.2 splice_donor_5th_base, intron
Scores
2
Splicing: ADA: 0.9956
2
Clinical Significance
Conservation
PhyloP100: 4.37
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 -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
?
Variant 6-32062152-C-T is Benign according to our data. Variant chr6-32062152-C-T is described in ClinVar as [Benign]. Clinvar id is 261154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32062152-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.7168+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000644971.2 | |||
TNXB | NM_019105.8 | c.7168+5G>A | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNXB | ENST00000644971.2 | c.7168+5G>A | splice_donor_5th_base_variant, intron_variant | NM_001365276.2 | |||||
TNXB | ENST00000375244.7 | c.7168+5G>A | splice_donor_5th_base_variant, intron_variant | 5 | |||||
TNXB | ENST00000647633.1 | c.7909+5G>A | splice_donor_5th_base_variant, intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0432 AC: 6579AN: 152232Hom.: 190 Cov.: 32
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GnomAD3 exomes AF: 0.0251 AC: 6118AN: 243866Hom.: 129 AF XY: 0.0233 AC XY: 3099AN XY: 133024
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GnomAD4 exome AF: 0.0357 AC: 52050AN: 1456986Hom.: 1150 Cov.: 33 AF XY: 0.0338 AC XY: 24476AN XY: 724008
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GnomAD4 genome ? AF: 0.0432 AC: 6585AN: 152350Hom.: 189 Cov.: 32 AF XY: 0.0408 AC XY: 3042AN XY: 74498
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ClinVar
Significance: Benign
Submissions summary: Benign:4
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 | - | - - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 14, 2022 | - - |
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 21, 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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at