rs12784975

Positions:

chr10-96620380-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000339364.10(PIK3AP1):c.1913A>G(p.Lys638Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,944 control chromosomes in the GnomAD database, including 29,672 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2612 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27060 hom. )

Consequence

PIK3AP1
ENST00000339364.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.70

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011126697).

BP6

Variant 10-96620380-T-C is Benign according to our data. Variant chr10-96620380-T-C is described in ClinVar as [Benign]. Clinvar id is 1169953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIK3AP1	NM_152309.3 linkuse as main transcript	c.1913A>G	p.Lys638Arg	missense_variant	12/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.1913A>G	p.Lys638Arg	missense_variant	12/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.1379A>G	p.Lys460Arg	missense_variant	11/16		XP_005269556.1
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.1379A>G	p.Lys460Arg	missense_variant	13/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.1913A>G	p.Lys638Arg	missense_variant	12/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.710A>G	p.Lys237Arg	missense_variant	5/10	1		ENSP00000360150		Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.1379A>G	p.Lys460Arg	missense_variant	11/16	2		ENSP00000360151		Q6ZUJ8-2
PIK3AP1	ENST00000489982.1 linkuse as main transcript	n.32A>G		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26461

AN:

152078

Hom.:

2611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.188

AC:

47224

AN:

251030

Hom.:

5355

AF XY:

0.181

AC XY:

24594

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.186

AC:

272161

AN:

1461748

Hom.:

27060

Cov.:

AF XY:

0.184

AC XY:

133448

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.0860

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.174

AC:

26469

AN:

152196

Hom.:

2612

Cov.:

AF XY:

0.168

AC XY:

12533

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.0966

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.190

Hom.:

4675

Bravo

AF:

0.190

TwinsUK

AF:

0.201

AC:

744

ALSPAC

AF:

0.188

AC:

723

ESP6500AA

AF:

0.123

AC:

542

ESP6500EA

AF:

0.195

AC:

1676

ExAC

AF:

0.178

AC:

21675

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.201

EpiControl

AF:

0.205

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile spasms

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.89

L;.;.

MutationTaster

Benign

0.0060

P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.063

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.053

MPC

0.46

ClinPred

0.0044

GERP RS

3.6

Varity_R

0.065

gMVP

0.13

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