rs649610

chr18-41992294-G-Achr18-41992294-G-Cchr18-41992294-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002647.4(PIK3C3):c.715-976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,970 control chromosomes in the GnomAD database, including 20,158 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 (20158 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C3	NM_002647.4	c.715-976G>A		intron_variant		ENST00000262039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C3	ENST00000262039.9	c.715-976G>A		intron_variant		1	NM_002647.4	P1
PIK3C3	ENST00000398870.7	c.526-976G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74809 AN: 151852 Hom.: 20112 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.493 AC: 74916 AN: 151970 Hom.: 20158 Cov.: 32 AF XY: 0.496 AC XY: 36813 AN XY: 74266

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.459

Alfa AF: 0.448 Hom.: 3070

Bravo AF: 0.514

Asia WGS AF: 0.588 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	12
Dann	Benign	0.68

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: rs649610; hg19: chr18-39572258;