rs142087930

chr10-96626826-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_152309.3(PIK3AP1):c.1551T>C(p.Asp517=) 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (0 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.262

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]

ACMG classification

Verdict is Benign. Variant got -17 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 [Likely_benign]. Clinvar id is 541760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.262 with no splicing effect.
• BS2: High AC in GnomAd at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.1551T>C	p.Asp517=	synonymous_variant	10/17	ENST00000339364.10
PIK3AP1	XM_011539248.2	c.1551T>C	p.Asp517=	synonymous_variant	10/16
PIK3AP1	XM_005269499.2	c.1017T>C	p.Asp339=	synonymous_variant	9/16
PIK3AP1	XM_047424566.1	c.1017T>C	p.Asp339=	synonymous_variant	11/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1551T>C	p.Asp517=	synonymous_variant	10/17	1	NM_152309.3	P1
PIK3AP1	ENST00000371109.3	c.348T>C	p.Asp116=	synonymous_variant	3/10	1
PIK3AP1	ENST00000371110.6	c.1017T>C	p.Asp339=	synonymous_variant	9/16	2

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152262 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000515 AC XY: 70 AN XY: 135846

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.: 0 Cov.: 34 AF XY: 0.000725 AC XY: 527 AN XY: 727224

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: 72 AN: 152380 Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20 AN XY: 74518

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.: 0

Bravo AF: 0.000393

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Infantile spasms Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 02, 2024

- -

PIK3AP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 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	-0.84
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

Other links and lift over

dbSNP: rs142087930; hg19: chr10-98386583;