rs1983936348

Variant names:

• chr18-42033928-A-C
• rs1983936348
• NM_002647.4:c.1810A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-42033928-A-C
• chr18-42033928-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002647.4(PIK3C3):​c.1810A>C​(p.Ile604Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I604V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3C3 NM_002647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.51
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C3	NM_002647.4	c.1810A>C	p.Ile604Leu	missense_variant	Exon 16 of 25	ENST00000262039.9	NP_002638.2
PIK3C3	NM_001308020.2	c.1621A>C	p.Ile541Leu	missense_variant	Exon 15 of 24		NP_001294949.1
PIK3C3	XM_047437549.1	c.1810A>C	p.Ile604Leu	missense_variant	Exon 16 of 22		XP_047293505.1
PIK3C3	XM_047437550.1	c.1252A>C	p.Ile418Leu	missense_variant	Exon 14 of 23		XP_047293506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C3	ENST00000262039.9	c.1810A>C	p.Ile604Leu	missense_variant	Exon 16 of 25	1	NM_002647.4	ENSP00000262039.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.4	L;.;.
PhyloP100		8.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Uncertain	0.50
Sift	Benign	0.064	T;.;T
Sift4G	Benign	0.11	T;.;T
Polyphen		0.0	B;.;B
Vest4		0.56
MutPred		0.40		Loss of catalytic residue at P606 (P = 0.0334);.;.;
MVP		0.69
MPC		1.0
ClinPred		0.90	D
GERP RS		5.6
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.69
Mutation Taster		=39/61	disease causing

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: rs1983936348; hg19: chr18-39613892;