chr18-42067000-A-G

Variant names:

• chr18-42067000-A-G
• rs620052
• NM_002647.4:c.2524-388A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002647.4(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 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIK3C3	NM_002647.4	c.2524-388A>G		intron_variant	Intron 23 of 24	ENST00000262039.9	NP_002638.2
PIK3C3	NM_001308020.2	c.2335-388A>G		intron_variant	Intron 22 of 23		NP_001294949.1
PIK3C3	XM_047437550.1	c.1966-388A>G		intron_variant	Intron 21 of 22		XP_047293506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C3	ENST00000262039.9	c.2524-388A>G		intron_variant	Intron 23 of 24	1	NM_002647.4	ENSP00000262039.3

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

African (AFR) AF: 0.716 AC: 29633 AN: 41370

American (AMR) AF: 0.535 AC: 8155 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3762 AN: 5136

South Asian (SAS) AF: 0.551 AC: 2649 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4058 AN: 10522

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26059 AN: 67948

Other (OTH) AF: 0.473 AC: 999 AN: 2110

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs620052; hg19: chr18-39646964;