rs52911

chr18-41974975-G-Achr18-41974975-G-Cchr18-41974975-G-T

Variant summary

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

The NM_002647.4(PIK3C3):c.531+4519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,972 control chromosomes in the GnomAD database, including 19,775 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 0.49 (19775 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

PIK3C3 (HGNC:8974): (phosphatidylinositol 3-kinase catalytic subunit type 3) Enables 1-phosphatidylinositol-3-kinase activity. Involved in early endosome to late endosome transport and regulation of cytokinesis. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C3	NM_002647.4	c.531+4519G>A		intron_variant		ENST00000262039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C3	ENST00000262039.9	c.531+4519G>A		intron_variant		1	NM_002647.4	P1
PIK3C3	ENST00000398870.7	c.342+4519G>A		intron_variant		2
PIK3C3	ENST00000591011.1	c.394+4519G>A		intron_variant, NMD_transcript_variant		5
PIK3C3	ENST00000589550.1	n.366+4519G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74277 AN: 151854 Hom.: 19734 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.452

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.489 AC: 74376 AN: 151972 Hom.: 19775 Cov.: 32 AF XY: 0.492 AC XY: 36552 AN XY: 74266

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.456

Alfa AF: 0.431 Hom.: 4198

Bravo AF: 0.510

Asia WGS AF: 0.586 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.95
Dann	Benign	0.43

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: rs52911; hg19: chr18-39554939;