rs880348

Positions:

• chr10-96621689-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152309.3(PIK3AP1):​c.1736-1132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,238 control chromosomes in the GnomAD database, including 12,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12342 hom., cov: 32)
  • Exomes 𝑓: 0.44 (18 hom.)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

RPS2P36 (HGNC:36784): (ribosomal protein S2 pseudogene 36)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.1736-1132G>A		intron_variant		ENST00000339364.10	NP_689522.2
PIK3AP1	XM_005269499.2	c.1202-1132G>A		intron_variant			XP_005269556.1
PIK3AP1	XM_011539248.2	c.1736-1132G>A		intron_variant			XP_011537550.1
PIK3AP1	XM_047424566.1	c.1202-1132G>A		intron_variant			XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1736-1132G>A		intron_variant		1	NM_152309.3	ENSP00000339826	P1
PIK3AP1	ENST00000371109.3	c.533-1132G>A		intron_variant		1		ENSP00000360150
RPS2P36	ENST00000456516.1	n.19G>A		non_coding_transcript_exon_variant	1/1
PIK3AP1	ENST00000371110.6	c.1202-1132G>A		intron_variant		2		ENSP00000360151

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60494 AN: 151946 Hom.: 12340 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.436 AC: 75 AN: 172 Hom.: 18 Cov.: 0 AF XY: 0.471 AC XY: 48 AN XY: 102

Gnomad4 AFR exome AF: 0.375

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.398 AC: 60523 AN: 152066 Hom.: 12342 Cov.: 32 AF XY: 0.399 AC XY: 29665 AN XY: 74340

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.428

Alfa AF: 0.416 Hom.: 13070

Bravo AF: 0.405

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.7
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: rs880348; hg19: chr10-98381446;