rs647512

Positions:

• chr18-42059512-G-A
• chr18-42059512-G-C

Variant summary

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

The NM_002647.4(PIK3C3):​c.2432+1461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,954 control chromosomes in the GnomAD database, including 19,735 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 (19735 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C3	NM_002647.4	c.2432+1461G>A		intron_variant		ENST00000262039.9
PIK3C3	NM_001308020.2	c.2243+1461G>A		intron_variant
PIK3C3	XM_047437549.1	c.2264-5228G>A		intron_variant
PIK3C3	XM_047437550.1	c.1874+1461G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C3	ENST00000262039.9	c.2432+1461G>A		intron_variant		1	NM_002647.4	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74288 AN: 151836 Hom.: 19694 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.490 AC: 74387 AN: 151954 Hom.: 19735 Cov.: 32 AF XY: 0.492 AC XY: 36547 AN XY: 74270

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.457

Alfa AF: 0.375 Hom.: 2172

Bravo AF: 0.510

Asia WGS AF: 0.586 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0020
DANN	Benign	0.69

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: rs647512; hg19: chr18-39639476;