rs1131692243
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePP3_ModeratePP5
The NM_181523.3(PIK3R1):c.1748_1750del(p.Trp583del) variant causes a splice acceptor, coding sequence change involving the alteration of a conserved nucleotide. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
PIK3R1
NM_181523.3 splice_acceptor, coding_sequence
NM_181523.3 splice_acceptor, coding_sequence
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
PIK3R1 (HGNC:8979): (phosphoinositide-3-kinase regulatory subunit 1) Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.03126437 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9, offset of 0 (no position change), new splice context is: ttttcaaaactgtttttcAGgtt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 5-68295418-AGGT-A is Pathogenic according to our data. Variant chr5-68295418-AGGT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376263.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-68295418-AGGT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.1748_1750del | p.Trp583del | splice_acceptor_variant, coding_sequence_variant | 14/16 | ENST00000521381.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.1748_1750del | p.Trp583del | splice_acceptor_variant, coding_sequence_variant | 14/16 | 1 | NM_181523.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neoplasm Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
Vascular Malformations and Overgrowth Pathogenic:1
Pathogenic, no assertion criteria provided | research | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Nov 08, 2020 | This alteration is of apparent somatic mosaic etiology with strong supporting evidence including no discernible strand bias, in a region absent of repetition and sequence homology, with clean, high-quality reads, having a variant allele fraction >= 3% [PS2], is supported by well-established models demonstrating downstream impact of the variant on RNA structure, gene expression, or protein function [PS3], is either well-represented in cancer as identified in the COSMIC database with >=20 documented instances or considered to occur in a statistically significant hotspot or region according to cancerhotspots.org database [PM_CANCER], is in a non-repetitive region and results in a protein length change predicted to result in an in-frame protein product [PM4], and is at increased prevalence in our cohort, with >= 3 occurrences in unrelated individuals [PS4_Sup]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 5
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at