Variant rs74496843 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152309.3(PIK3AP1):c.1506T>C(p.Asp502Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,174 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 9 hom. )

Consequence

PIK3AP1
NM_152309.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-96626871-A-G is Benign according to our data. Variant chr10-96626871-A-G is described in ClinVar as [Benign]. Clinvar id is 474915.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00671 (1022/152348) while in subpopulation AFR AF= 0.0234 (974/41576). AF 95% confidence interval is 0.0222. There are 17 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1022 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3 linkuse as main transcript	c.1506T>C	p.Asp502Asp	synonymous_variant	10/17	ENST00000339364.10	NP_689522.2	Q6ZUJ8-1Q86YV3
PIK3AP1	XM_011539248.2 linkuse as main transcript	c.1506T>C	p.Asp502Asp	synonymous_variant	10/16		XP_011537550.1
PIK3AP1	XM_005269499.2 linkuse as main transcript	c.972T>C	p.Asp324Asp	synonymous_variant	9/16		XP_005269556.1	Q6ZUJ8-2
PIK3AP1	XM_047424566.1 linkuse as main transcript	c.972T>C	p.Asp324Asp	synonymous_variant	11/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIK3AP1	ENST00000339364.10 linkuse as main transcript	c.1506T>C	p.Asp502Asp	synonymous_variant	10/17	1	NM_152309.3	ENSP00000339826.5	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 linkuse as main transcript	c.303T>C	p.Asp101Asp	synonymous_variant	3/10	1		ENSP00000360150.3	Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 linkuse as main transcript	c.972T>C	p.Asp324Asp	synonymous_variant	9/16	2		ENSP00000360151.2	Q6ZUJ8-2

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1023

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00188

AC:

473

AN:

251286

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000722

AC:

1055

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

468

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00671

AC:

1022

AN:

152348

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

494

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00348

Hom.:

Bravo

AF:

0.00742

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Infantile spasms

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.55

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