rs199720844

chr10-96626882-G-A

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.1495C>T(p.Leu499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.108

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=-0.78).
• BP6: Variant 10-96626882-G-A is Benign according to our data. Variant chr10-96626882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.
• BS2: High AC in GnomAd at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.1495C>T	p.Leu499=	synonymous_variant	10/17	ENST00000339364.10
PIK3AP1	XM_011539248.2	c.1495C>T	p.Leu499=	synonymous_variant	10/16
PIK3AP1	XM_005269499.2	c.961C>T	p.Leu321=	synonymous_variant	9/16
PIK3AP1	XM_047424566.1	c.961C>T	p.Leu321=	synonymous_variant	11/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1495C>T	p.Leu499=	synonymous_variant	10/17	1	NM_152309.3	P1
PIK3AP1	ENST00000371109.3	c.292C>T	p.Leu98=	synonymous_variant	3/10	1
PIK3AP1	ENST00000371110.6	c.961C>T	p.Leu321=	synonymous_variant	9/16	2

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000876 AC: 22 AN: 251236 Hom.: 0 AF XY: 0.0000737 AC XY: 10 AN XY: 135766

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461788 Hom.: 1 Cov.: 34 AF XY: 0.0000440 AC XY: 32 AN XY: 727216

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20 AN XY: 74504

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000576 Hom.: 0

Bravo AF: 0.000325

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Infantile spasms Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 25, 2023

- -

PIK3AP1-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 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	-0.78
Cadd	Benign	2.5
Dann	Benign	0.79

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: rs199720844; hg19: chr10-98386639;