Variant 18-42004523-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002647.4(PIK3C3):c.1152G>A(p.Leu384Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,592,914 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 22 hom. )

Consequence

PIK3C3
NM_002647.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Variant links:

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]

PIK3C3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 18-42004523-G-A is Benign according to our data. Variant chr18-42004523-G-A is described in ClinVar as [Benign]. Clinvar id is 783802.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00899 (1368/152246) while in subpopulation AFR AF= 0.0316 (1314/41530). AF 95% confidence interval is 0.0302. There are 18 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1368 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C3	NM_002647.4 linkuse as main transcript	c.1152G>A	p.Leu384Leu	synonymous_variant	10/25	ENST00000262039.9	NP_002638.2	Q8NEB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C3	ENST00000262039.9 linkuse as main transcript	c.1152G>A	p.Leu384Leu	synonymous_variant	10/25	1	NM_002647.4	ENSP00000262039.3		Q8NEB9
PIK3C3	ENST00000398870.7 linkuse as main transcript	c.963G>A	p.Leu321Leu	synonymous_variant	9/24	2		ENSP00000381845.2		A8MYT4

Frequencies

GnomAD3 genomes

AF:

0.00897

AC:

1365

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00257

AC:

586

AN:

227970

Hom.:

AF XY:

0.00183

AC XY:

226

AN XY:

123426

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000652

Gnomad OTH exome

AF:

0.000734

GnomAD4 exome

AF:

0.000852

AC:

1227

AN:

1440668

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

529

AN XY:

716162

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000733

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

AF:

0.00899

AC:

1368

AN:

152246

Hom.:

Cov.:

AF XY:

0.00844

AC XY:

628

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00540

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.9

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over