rs150666185

Positions:

chr10-96656857-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000339364.10(PIK3AP1):c.508C>A(p.Pro170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P170L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PIK3AP1
ENST00000339364.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021992773).

BS2

High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIK3AP1	NM_152309.3 linkuse as main transcript	c.508C>A	p.Pro170Thr	missense_variant	3/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.508C>A	p.Pro170Thr	missense_variant	3/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.-27C>A		5_prime_UTR_variant	2/16		XP_005269556.1
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.-27C>A		5_prime_UTR_variant	4/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.508C>A	p.Pro170Thr	missense_variant	3/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.-27C>A		5_prime_UTR_variant	2/16	2		ENSP00000360151		Q6ZUJ8-2
PIK3AP1	ENST00000468783.1 linkuse as main transcript	n.154C>A		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251452

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000289

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:

0.00000752

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000671

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

AF:

0.000138

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000555

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Nov 27, 2023

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 170 of the PIK3AP1 protein (p.Pro170Thr). This variant is present in population databases (rs150666185, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 582895). 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 tolerated. 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

0.070

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.1

DANN

Benign

0.77

DEOGEN2

Benign

0.13

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.59

M_CAP

Benign

0.0060

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.45

REVEL

Benign

0.032

Sift

Benign

0.23

Sift4G

Benign

0.068

Polyphen

0.16

Vest4

0.088

MVP

0.13

MPC

0.60

ClinPred

0.011

GERP RS

4.1

Varity_R

0.043

gMVP

0.29

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