1-9710513-G-T

Variant names:

• chr1-9710513-G-T
• rs143116020
• NM_005026.5:c.58G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005026.5(PIK3CD):​c.58G>T​(p.Val20Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V20I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIK3CD NM_005026.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76
• Publications: 0 publications found

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]

PIK3CD Gene-Disease associations (from GenCC):

• immunodeficiency 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• immunodeficiency 14b, autosomal recessive

  Inheritance: Unknown, AR Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• activated PI3K-delta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34690544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005026.5. 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
	PIK3CD	NM_005026.5	MANE Select	c.58G>T	p.Val20Phe	missense	Exon 3 of 24	NP_005017.3
	PIK3CD	NM_001437546.1		c.58G>T	p.Val20Phe	missense	Exon 2 of 23	NP_001424475.1	A0A2K8FKV1
	PIK3CD	NM_001350234.2		c.58G>T	p.Val20Phe	missense	Exon 3 of 24	NP_001337163.1	B7ZM44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.58G>T	p.Val20Phe	missense	Exon 3 of 24	ENSP00000366563.4	O00329-1
	PIK3CD	ENST00000361110.6	TSL:1	c.58G>T	p.Val20Phe	missense	Exon 2 of 23	ENSP00000354410.2	F8W9P4
	PIK3CD	ENST00000892288.1		c.58G>T	p.Val20Phe	missense	Exon 3 of 24	ENSP00000562347.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.36
MutPred		0.56		Loss of stability (P = 0.1679)
MVP		0.70
MPC		2.0
ClinPred		0.94	D
GERP RS		4.5
PromoterAI		-0.044	Neutral
Varity_R		0.29
gMVP		0.98
Mutation Taster		=63/37	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: rs143116020; hg19: chr1-9770571;