Variant 10-96609806-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152309.3(PIK3AP1):c.2076A>G(p.Gly692=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,614,066 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

PIK3AP1
NM_152309.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.604

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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 10-96609806-T-C is Benign according to our data. Variant chr10-96609806-T-C is described in ClinVar as [Benign]. Clinvar id is 474919.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.604 with no splicing effect.

BS2

High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3AP1	NM_152309.3 linkuse as main transcript	c.2076A>G	p.Gly692=	synonymous_variant	14/17	ENST00000339364.10
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.2076A>G	p.Gly692=	synonymous_variant	14/16
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.1542A>G	p.Gly514=	synonymous_variant	13/16
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.1542A>G	p.Gly514=	synonymous_variant	15/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.2076A>G	p.Gly692=	synonymous_variant	14/17	1	NM_152309.3	P1	Q6ZUJ8-1

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

248

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00149

AC:

374

AN:

251372

Hom.:

AF XY:

0.00162

AC XY:

220

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00230

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00210

AC:

3074

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1507

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00248

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00163

AC:

248

AN:

152256

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00115

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00207

ClinVar

Significance: Benign/Likely 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

Invitae

Jan 17, 2024

- -

PIK3AP1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.5

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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