rs200438334

Variant names:

• chr18-42004549-ATTAT-A
• rs200438334
• NM_002647.4:c.1170+14_1170+17delTATT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002647.4(PIK3C3):​c.1170+14_1170+17delTATT 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
• Publications: 0 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: Likely_benign. The variant received -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 VariationId is 782554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 748 AD gene.

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.1170+14_1170+17delTATT		intron	N/A	NP_002638.2
	PIK3C3	NM_001308020.2		c.981+14_981+17delTATT		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.1170+9_1170+12delTTAT		intron	N/A	ENSP00000262039.3	Q8NEB9
	PIK3C3	ENST00000858068.1		c.1170+9_1170+12delTTAT		intron	N/A	ENSP00000528127.1
	PIK3C3	ENST00000858070.1		c.1170+9_1170+12delTTAT		intron	N/A	ENSP00000528129.1

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

GnomAD2 exomes AF: 0.00514 AC: 1127 AN: 219156 AF XY: 0.00569

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 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

African (AFR) AF: 0.000897 AC: 28 AN: 31228

American (AMR) AF: 0.00599 AC: 206 AN: 34400

Ashkenazi Jewish (ASJ) AF: 0.00200 AC: 48 AN: 23998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00242 AC: 195 AN: 80552

European-Finnish (FIN) AF: 0.00218 AC: 115 AN: 52680

Middle Eastern (MID) AF: 0.00937 AC: 52 AN: 5550

European-Non Finnish (NFE) AF: 0.00755 AC: 8292 AN: 1098626

Other (OTH) AF: 0.00646 AC: 380 AN: 58788

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

African (AFR) AF: 0.00145 AC: 60 AN: 41510

American (AMR) AF: 0.00458 AC: 70 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00809 AC: 550 AN: 68012

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00597 Hom.: 0

Bravo AF: 0.00528

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism

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: rs200438334; hg19: chr18-39584513;