rs797045952
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015559.3(SETBP1):c.1821del(p.Ser608AlafsTer22) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SETBP1
NM_015559.3 frameshift
NM_015559.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.88
Genes affected
SETBP1 (HGNC:15573): (SET binding protein 1) This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-44951159-AC-A is Pathogenic according to our data. Variant chr18-44951159-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 212152.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-44951159-AC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETBP1 | NM_015559.3 | c.1821del | p.Ser608AlafsTer22 | frameshift_variant | 4/6 | ENST00000649279.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETBP1 | ENST00000649279.2 | c.1821del | p.Ser608AlafsTer22 | frameshift_variant | 4/6 | NM_015559.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 29 Pathogenic:1
Pathogenic, no assertion criteria provided | provider interpretation | GenomeConnect - Simons Searchlight | Jul 14, 2017 | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-07-14 and interpreted as Pathogenic. Variant was initially reported on 2014-05-23 by GTR ID of laboratory name 1238. The reporting laboratory might also submit to ClinVar. - |
Schinzel-Giedion syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 03, 2014 | - - |
Computational scores
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Calibrated prediction
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Prediction
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