10-96602305-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152309.3(PIK3AP1):​c.2335G>C​(p.Val779Leu) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PIK3AP1
NM_152309.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15342048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIK3AP1NM_152309.3 linkuse as main transcriptc.2335G>C p.Val779Leu missense_variant 16/17 ENST00000339364.10 NP_689522.2
LOC105378443XR_946220.4 linkuse as main transcriptn.1447-5371C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIK3AP1ENST00000339364.10 linkuse as main transcriptc.2335G>C p.Val779Leu missense_variant 16/171 NM_152309.3 ENSP00000339826 P1Q6ZUJ8-1
PIK3AP1ENST00000371109.3 linkuse as main transcriptc.1132G>C p.Val378Leu missense_variant 9/101 ENSP00000360150 Q6ZUJ8-3
PIK3AP1ENST00000371110.6 linkuse as main transcriptc.1801G>C p.Val601Leu missense_variant 15/162 ENSP00000360151 Q6ZUJ8-2
PIK3AP1ENST00000467625.5 linkuse as main transcriptn.532G>C non_coding_transcript_exon_variant 5/63

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 13, 2022In 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 779 of the PIK3AP1 protein (p.Val779Leu). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
T;.;.
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.099
FATHMM_MKL
Benign
0.66
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
0.73
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.72
N;N;N
REVEL
Benign
0.054
Sift
Benign
0.10
T;T;D
Sift4G
Benign
0.11
T;T;T
Polyphen
0.50
P;.;B
Vest4
0.27
MutPred
0.28
Gain of glycosylation at P777 (P = 0.0779);.;.;
MVP
0.39
MPC
0.88
ClinPred
0.39
T
GERP RS
3.0
Varity_R
0.049
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-98362062; API