Variant 10-96602286-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152309.3(PIK3AP1):c.2354C>T(p.Ser785Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,170 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIK3AP1
NM_152309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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]

PIK3AP1 links:

LOC105378443 (HGNC:):

LOC105378443 links:

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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=0.22935122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3 linkuse as main transcript	c.2354C>T	p.Ser785Leu	missense_variant	16/17	ENST00000339364.10	NP_689522.2
LOC105378443	XR_946220.4 linkuse as main transcript	n.1447-5390G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.2354C>T	p.Ser785Leu	missense_variant	16/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.1151C>T	p.Ser384Leu	missense_variant	9/10	1		ENSP00000360150		Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.1820C>T	p.Ser607Leu	missense_variant	15/16	2		ENSP00000360151		Q6ZUJ8-2
PIK3AP1	ENST00000467625.5 linkuse as main transcript	n.551C>T		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244324

Hom.:

AF XY:

0.00000756

AC XY:

AN XY:

132298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1451170

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000471

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.:

ExAC

AF:

0.00000824

AC:

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

Sep 08, 2021

This sequence change replaces serine with leucine at codon 785 of the PIK3AP1 protein (p.Ser785Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs769596130, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.57

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.99

D;.;D

Vest4

0.29

MutPred

0.21

Loss of phosphorylation at S785 (P = 0.0017);.;.;

MVP

0.41

MPC

1.4

ClinPred

0.64

GERP RS

4.2

Varity_R

0.072

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over