10-96623472-C-T

Position:

chr10-96623472-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_152309.3(PIK3AP1):c.1735G>A(p.Gly579Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000378 in 1,609,772 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 2 hom. )

Consequence

PIK3AP1
NM_152309.3 missense, splice_region

Scores

Splicing: ADA: 0.9983

Clinical Significance

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

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

BP6

Variant 10-96623472-C-T is Benign according to our data. Variant chr10-96623472-C-T is described in ClinVar as [Benign]. Clinvar id is 541757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIK3AP1	NM_152309.3 linkuse as main transcript	c.1735G>A	p.Gly579Arg	missense_variant, splice_region_variant	11/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.1735G>A	p.Gly579Arg	missense_variant, splice_region_variant	11/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.1201G>A	p.Gly401Arg	missense_variant, splice_region_variant	10/16		XP_005269556.1
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.1201G>A	p.Gly401Arg	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>A	p.Gly579Arg	missense_variant, splice_region_variant	11/17	1	NM_152309.3	ENSP00000339826	P1	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.532G>A	p.Gly178Arg	missense_variant, splice_region_variant	4/10	1		ENSP00000360150		Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.1201G>A	p.Gly401Arg	missense_variant, splice_region_variant	10/16	2		ENSP00000360151		Q6ZUJ8-2

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000709

AC:

178

AN:

251216

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000370

AC:

540

AN:

1457616

Hom.:

Cov.:

AF XY:

0.000374

AC XY:

271

AN XY:

725356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000532

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.000447

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000768

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000576

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Nov 02, 2023

- -

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

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.35

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.053

T;T;T

Sift4G

Benign

0.073

T;T;T

Polyphen

0.28

B;.;P

Vest4

0.14

MutPred

0.18

Gain of MoRF binding (P = 0.0123);.;.;

MVP

0.19

MPC

0.66

ClinPred

0.046

GERP RS

5.6

Varity_R

0.095

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.88

SpliceAI score (max)

0.030

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