rs593248

Variant names:

• chr18-42034146-G-A
• rs593248
• NM_002647.4:c.1839+189G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-42034146-G-A
• chr18-42034146-G-T

Variant summary

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

The NM_002647.4(PIK3C3):​c.1839+189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,026 control chromosomes in the GnomAD database, including 21,405 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 0.50 (21405 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	NM_002647.4	MANE Select	c.1839+189G>A		intron	N/A	NP_002638.2
	PIK3C3	NM_001308020.2		c.1650+189G>A		intron	N/A	NP_001294949.1	A8MYT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	ENST00000262039.9	TSL:1 MANE Select	c.1839+189G>A		intron	N/A	ENSP00000262039.3	Q8NEB9
	PIK3C3	ENST00000858068.1		c.1839+189G>A		intron	N/A	ENSP00000528127.1
	PIK3C3	ENST00000858070.1		c.1839+189G>A		intron	N/A	ENSP00000528129.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76607 AN: 151908 Hom.: 21354 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.505 AC: 76720 AN: 152026 Hom.: 21405 Cov.: 32 AF XY: 0.507 AC XY: 37649 AN XY: 74290

African (AFR) AF: 0.751 AC: 31186 AN: 41508

American (AMR) AF: 0.531 AC: 8100 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3464

East Asian (EAS) AF: 0.611 AC: 3161 AN: 5176

South Asian (SAS) AF: 0.511 AC: 2457 AN: 4810

European-Finnish (FIN) AF: 0.379 AC: 3998 AN: 10542

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.370 AC: 25139 AN: 67942

Other (OTH) AF: 0.466 AC: 985 AN: 2114

Alfa AF: 0.439 Hom.: 4963

Bravo AF: 0.526

Asia WGS AF: 0.591 AC: 2057 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.55
PhyloP100		-1.4
PromoterAI		0.010	Neutral
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: rs593248; hg19: chr18-39614110;