rs620052

Positions:

• chr18-42067000-A-G
• chr18-42067000-A-T

Variant summary

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

The ENST00000262039.9(PIK3C3):​c.2524-388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,814 control chromosomes in the GnomAD database, including 21,188 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 0.51 (21188 hom., cov: 31)
• Consequence: PIK3C3 ENST00000262039.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C3	NM_002647.4	c.2524-388A>G		intron_variant		ENST00000262039.9	NP_002638.2
PIK3C3	NM_001308020.2	c.2335-388A>G		intron_variant			NP_001294949.1
PIK3C3	XM_047437550.1	c.1966-388A>G		intron_variant			XP_047293506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C3	ENST00000262039.9	c.2524-388A>G		intron_variant		1	NM_002647.4	ENSP00000262039	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76918 AN: 151696 Hom.: 21144 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.507 AC: 77024 AN: 151814 Hom.: 21188 Cov.: 31 AF XY: 0.511 AC XY: 37930 AN XY: 74198

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.473

Alfa AF: 0.444 Hom.: 2532

Bravo AF: 0.528

Asia WGS AF: 0.668 AC: 2318 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.52

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: rs620052; hg19: chr18-39646964;