rs371984369

Variant names:

• chr18-41955344-A-G
• rs371984369
• NM_002647.4:c.53A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-41955344-A-G
• chr18-41955344-A-T

Variant summary

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

The NM_002647.4(PIK3C3):​c.53A>G​(p.Asn18Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PIK3C3 NM_002647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• 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 0 ACMG points.

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.53A>G	p.Asn18Ser	missense	Exon 1 of 25	NP_002638.2
	PIK3C3	NM_001308020.2		c.53A>G	p.Asn18Ser	missense	Exon 1 of 24	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.53A>G	p.Asn18Ser	missense	Exon 1 of 25	ENSP00000262039.3	Q8NEB9
	PIK3C3	ENST00000586545.5	TSL:1	c.53A>G	p.Asn18Ser	missense	Exon 1 of 4	ENSP00000465621.1	K7EKH3
	PIK3C3	ENST00000858068.1		c.53A>G	p.Asn18Ser	missense	Exon 1 of 25	ENSP00000528127.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250782 AF XY: 0.00

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461188 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726922

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111636

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.25
Sift	Benign	0.40	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.72
MVP		0.76
MPC		0.16
ClinPred		0.89	D
GERP RS		5.8
PromoterAI		-0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.41
Mutation Taster		=48/52	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: rs371984369; hg19: chr18-39535309;