18-42004544-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002647.4(PIK3C3):c.1170+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,429,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PIK3C3
NM_002647.4 splice_donor_region, intron
NM_002647.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00005506
2
Clinical Significance
Conservation
PhyloP100: 0.0720
Genes affected
PIK3C3 (HGNC:8974): (phosphatidylinositol 3-kinase catalytic subunit type 3) Enables 1-phosphatidylinositol-3-kinase activity. Involved in early endosome to late endosome transport and regulation of cytokinesis. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3C3 | NM_002647.4 | c.1170+3G>A | splice_donor_region_variant, intron_variant | ENST00000262039.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3C3 | ENST00000262039.9 | c.1170+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_002647.4 | P1 | |||
PIK3C3 | ENST00000398870.7 | c.981+3G>A | splice_donor_region_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152046Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.00000451 AC: 1AN: 221938Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 120392
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GnomAD4 exome AF: 0.00000280 AC: 4AN: 1429320Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1AN XY: 710234
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 25, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at