rs374140006

Positions:

• chr5-68279651-C-A
• chr5-68279651-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_181523.3(PIK3R1):​c.552C>A​(p.Asp184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3R1 NM_181523.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

Genes affected

PIK3R1 (HGNC:8979): (phosphoinositide-3-kinase regulatory subunit 1) Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PIK3R1. . Gene score misZ 2.7206 (greater than the threshold 3.09). Trascript score misZ 3.4358 (greater than threshold 3.09). GenCC has associacion of gene with agammaglobulinemia 7, autosomal recessive, autosomal agammaglobulinemia, immunodeficiency 36, SHORT syndrome, activated PI3K-delta syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2504936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.552C>A	p.Asp184Glu	missense_variant	5/16	ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.552C>A	p.Asp184Glu	missense_variant	5/16	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.37
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.34	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.48	T;T;T
Sift4G	Benign	1.0	T;T;D
Polyphen		0.031	B;B;.
Vest4		0.92
MutPred		0.55		Gain of methylation at K187 (P = 0.0859);Gain of methylation at K187 (P = 0.0859);.;
MVP		0.74
MPC		0.16
ClinPred		0.14	T
GERP RS		-7.1
Varity_R		0.15
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-67575479;