Genetic Variant NM_152309.3:c.1551T>C (chr10-96626826-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_152309.3(PIK3AP1):c.1551T>C(p.Asp517Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

PIK3AP1
NM_152309.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.262

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=-0.84).

BP6

Variant 10-96626826-A-G is Benign according to our data. Variant chr10-96626826-A-G is described in ClinVar as [Benign]. Clinvar id is 541760.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.262 with no splicing effect.

BS2

High AC in GnomAd4 at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3 link	c.1551T>C	p.Asp517Asp	synonymous_variant	Exon 10 of 17	ENST00000339364.10	NP_689522.2	Q6ZUJ8-1Q86YV3
PIK3AP1	XM_011539248.2 link	c.1551T>C	p.Asp517Asp	synonymous_variant	Exon 10 of 16		XP_011537550.1
PIK3AP1	XM_005269499.2 link	c.1017T>C	p.Asp339Asp	synonymous_variant	Exon 9 of 16		XP_005269556.1	Q6ZUJ8-2
PIK3AP1	XM_047424566.1 link	c.1017T>C	p.Asp339Asp	synonymous_variant	Exon 11 of 18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIK3AP1	ENST00000339364.10 link	c.1551T>C	p.Asp517Asp	synonymous_variant	Exon 10 of 17	1	NM_152309.3	ENSP00000339826.5	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 link	c.348T>C	p.Asp116Asp	synonymous_variant	Exon 3 of 10	1		ENSP00000360150.3	Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 link	c.1017T>C	p.Asp339Asp	synonymous_variant	Exon 9 of 16	2		ENSP00000360151.2	Q6ZUJ8-2

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000513

AC:

129

AN:

251364

Hom.:

AF XY:

0.000515

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.000139

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000763

AC:

1116

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

527

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.000954

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000473

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000518

Hom.:

Bravo

AF:

0.000393

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Infantile spasms

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PIK3AP1-related disorder

Benign:1

Apr 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.84

CADD

Benign

1.8

DANN

Benign

0.40

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