1-9710512-C-A

Variant names:

• chr1-9710512-C-A
• rs376606452
• NM_005026.5:c.57C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005026.5(PIK3CD):​c.57C>A​(p.Ser19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: PIK3CD NM_005026.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

Genes affected

PIK3CD (HGNC:8977): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049467146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.57C>A	p.Ser19Arg	missense_variant	Exon 3 of 24	ENST00000377346.9	NP_005017.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9	c.57C>A	p.Ser19Arg	missense_variant	Exon 3 of 24	1	NM_005026.5	ENSP00000366563.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;T;T;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.51	.;T;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.049	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.65	.;.;N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;.;N;.;N
REVEL	Benign	0.035
Sift	Benign	0.18	T;.;T;.;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.0030	B;.;B;B;.
Vest4		0.16
MutPred		0.43		Loss of methylation at K14 (P = 0.0803);Loss of methylation at K14 (P = 0.0803);Loss of methylation at K14 (P = 0.0803);Loss of methylation at K14 (P = 0.0803);Loss of methylation at K14 (P = 0.0803);
MVP		0.45
MPC		1.0
ClinPred		0.13	T
GERP RS		1.9
Varity_R		0.094
gMVP		0.62

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: rs376606452; hg19: chr1-9770570;