rs145525421

Positions:

chr10-96628457-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000339364.10(PIK3AP1):c.1412T>A(p.Ile471Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,526 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

PIK3AP1
ENST00000339364.10 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0690

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008630097).

BP6

Variant 10-96628457-A-T is Benign according to our data. Variant chr10-96628457-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 541753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIK3AP1	NM_152309.3 linkuse as main transcript	c.1412T>A	p.Ile471Asn	missense_variant	9/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.1412T>A	p.Ile471Asn	missense_variant	9/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.878T>A	p.Ile293Asn	missense_variant	8/16		XP_005269556.1
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.878T>A	p.Ile293Asn	missense_variant	10/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.1412T>A	p.Ile471Asn	missense_variant	9/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.209T>A	p.Ile70Asn	missense_variant	2/10	1		ENSP00000360150		Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.878T>A	p.Ile293Asn	missense_variant	8/16	2		ENSP00000360151		Q6ZUJ8-2
PIK3AP1	ENST00000468783.1 linkuse as main transcript	n.1058T>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251244

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000896

AC:

131

AN:

1461296

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

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:

0.0000270

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000552

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000631

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile spasms

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 07, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.18

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.030

Sift

Benign

0.031

D;D;D

Sift4G

Benign

0.23

T;T;T

Polyphen

0.37

B;.;P

Vest4

0.17

MVP

0.12

MPC

1.0

ClinPred

0.015

GERP RS

0.40

Varity_R

0.048

gMVP

0.21

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