10-96602298-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_152309.3(PIK3AP1):c.2342C>T(p.Pro781Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,605,546 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PIK3AP1
NM_152309.3 missense
NM_152309.3 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34000224).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.2342C>T | p.Pro781Leu | missense_variant | 16/17 | ENST00000339364.10 | NP_689522.2 | |
LOC105378443 | XR_946220.4 | n.1447-5378G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.2342C>T | p.Pro781Leu | missense_variant | 16/17 | 1 | NM_152309.3 | ENSP00000339826 | P1 | |
PIK3AP1 | ENST00000371109.3 | c.1139C>T | p.Pro380Leu | missense_variant | 9/10 | 1 | ENSP00000360150 | |||
PIK3AP1 | ENST00000371110.6 | c.1808C>T | p.Pro603Leu | missense_variant | 15/16 | 2 | ENSP00000360151 | |||
PIK3AP1 | ENST00000467625.5 | n.539C>T | non_coding_transcript_exon_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1453406Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723138
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 03, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 781 of the PIK3AP1 protein (p.Pro781Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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