rs1555475794
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_005861.4(STUB1):c.*240T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
STUB1
NM_005861.4 3_prime_UTR
NM_005861.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.53
Genes affected
JMJD8 (HGNC:14148): (jumonji domain containing 8) Involved in several processes, including positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of sprouting angiogenesis; and regulation of glycolytic process. Located in endoplasmic reticulum lumen and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
STUB1 (HGNC:11427): (STIP1 homology and U-box containing protein 1) This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-682729-T-C is Pathogenic according to our data. Variant chr16-682729-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 522378.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JMJD8 | NM_001005920.4 | c.*65A>G | 3_prime_UTR_variant | 9/9 | ENST00000609261.6 | ||
STUB1 | NM_005861.4 | c.*240T>C | 3_prime_UTR_variant | 7/7 | ENST00000219548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STUB1 | ENST00000219548.9 | c.*240T>C | 3_prime_UTR_variant | 7/7 | 1 | NM_005861.4 | P1 | ||
JMJD8 | ENST00000609261.6 | c.*65A>G | 3_prime_UTR_variant | 9/9 | 1 | NM_001005920.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 16 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | University of Uludag Hospital, Genetic Diseases Diagnostic Center, University of Uludag | Feb 08, 2018 | Drastically low levels of STUB1 protein in patients. Not present in any database. Absent from controls and located in a highly conserved region of the gene. Cosegregation with disease in multiple affected family members (3 affected patients) in the STUB1 gene definitively known to cause SCAR16. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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