Variant rs144966728 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152309.3(PIK3AP1):c.1735G>T(p.Gly579Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,457,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIK3AP1
NM_152309.3 missense, splice_region

Scores

Splicing: ADA: 0.9997

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIK3AP1	NM_152309.3 linkuse as main transcript	c.1735G>T	p.Gly579Trp	missense_variant, splice_region_variant	11/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.1735G>T	p.Gly579Trp	missense_variant, splice_region_variant	11/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.1201G>T	p.Gly401Trp	missense_variant, splice_region_variant	10/16		XP_005269556.1
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.1201G>T	p.Gly401Trp	missense_variant, splice_region_variant	12/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.1735G>T	p.Gly579Trp	missense_variant, splice_region_variant	11/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.532G>T	p.Gly178Trp	missense_variant, splice_region_variant	4/10	1		ENSP00000360150		Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.1201G>T	p.Gly401Trp	missense_variant, splice_region_variant	10/16	2		ENSP00000360151		Q6ZUJ8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725358

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.97

D;.;D

Vest4

0.33

MutPred

0.27

Loss of relative solvent accessibility (P = 0.0186);.;.;

MVP

0.23

MPC

1.0

ClinPred

0.72

GERP RS

5.6

Varity_R

0.12

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over