10-96602301-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152309.3(PIK3AP1):​c.2339C>T​(p.Pro780Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PIK3AP1
NM_152309.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98
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]

Genome browser will be placed here

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=0.34996203).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIK3AP1NM_152309.3 linkuse as main transcriptc.2339C>T p.Pro780Leu missense_variant 16/17 ENST00000339364.10 NP_689522.2
LOC105378443XR_946220.4 linkuse as main transcriptn.1447-5375G>A 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.2339C>T p.Pro780Leu missense_variant 16/171 NM_152309.3 ENSP00000339826 P1Q6ZUJ8-1
PIK3AP1ENST00000371109.3 linkuse as main transcriptc.1136C>T p.Pro379Leu missense_variant 9/101 ENSP00000360150 Q6ZUJ8-3
PIK3AP1ENST00000371110.6 linkuse as main transcriptc.1805C>T p.Pro602Leu missense_variant 15/162 ENSP00000360151 Q6ZUJ8-2
PIK3AP1ENST00000467625.5 linkuse as main transcriptn.536C>T non_coding_transcript_exon_variant 5/63

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1452456
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722694
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.057
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
D;.;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.1
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0070
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.49
MutPred
0.24
Loss of catalytic residue at P780 (P = 0.0132);.;.;
MVP
0.34
MPC
1.5
ClinPred
0.95
D
GERP RS
4.2
Varity_R
0.19
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr10-98362058; API