18-42004549-ATTAT-A

Position:

• chr18-42004549-ATTAT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002647.4(PIK3C3):​c.1170+14_1170+17del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 1,577,394 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (41 hom.)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.770

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 18-42004549-ATTAT-A is Benign according to our data. Variant chr18-42004549-ATTAT-A is described in ClinVar as [Benign]. Clinvar id is 782554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C3	NM_002647.4	c.1170+14_1170+17del		intron_variant		ENST00000262039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C3	ENST00000262039.9	c.1170+14_1170+17del		intron_variant		1	NM_002647.4	P1
PIK3C3	ENST00000398870.7	c.981+14_981+17del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00492 AC: 749 AN: 152088 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00810

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00514 AC: 1127 AN: 219156 Hom.: 4 AF XY: 0.00569 AC XY: 677 AN XY: 118888

Gnomad AFR exome AF: 0.00109

Gnomad AMR exome AF: 0.00641

Gnomad ASJ exome AF: 0.00236

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00258

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.00767

Gnomad OTH exome AF: 0.00643

GnomAD4 exome AF: 0.00654 AC: 9316 AN: 1425188 Hom.: 41 AF XY: 0.00653 AC XY: 4625 AN XY: 708104

Gnomad4 AFR exome AF: 0.000897

Gnomad4 AMR exome AF: 0.00599

Gnomad4 ASJ exome AF: 0.00200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.00218

Gnomad4 NFE exome AF: 0.00755

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152206 Hom.: 4 Cov.: 32 AF XY: 0.00451 AC XY: 336 AN XY: 74420

Gnomad4 AFR AF: 0.00145

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00809

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00597 Hom.: 0

Bravo AF: 0.00528

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs200438334; hg19: chr18-39584513;