chr22-31291037-C-T

Variant names:

• chr22-31291037-C-T
• rs746269728
• NM_052880.5:c.235G>A

Variant summary

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

The NM_052880.5(PIK3IP1):​c.235G>A​(p.Gly79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIK3IP1 NM_052880.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

PIK3IP1 (HGNC:24942): (phosphoinositide-3-kinase interacting protein 1) Enables phosphatidylinositol 3-kinase catalytic subunit binding activity. Involved in negative regulation of phosphatidylinositol 3-kinase activity and negative regulation of phosphatidylinositol 3-kinase signaling. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052880.5. 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
	PIK3IP1	NM_052880.5	MANE Select	c.235G>A	p.Gly79Arg	missense	Exon 3 of 6	NP_443112.2	Q96FE7-1
	PIK3IP1	NM_001135911.1		c.235G>A	p.Gly79Arg	missense	Exon 3 of 5	NP_001129383.1	Q96FE7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3IP1	ENST00000215912.10	TSL:1 MANE Select	c.235G>A	p.Gly79Arg	missense	Exon 3 of 6	ENSP00000215912.4	Q96FE7-1
	PIK3IP1	ENST00000402249.7	TSL:1	c.235G>A	p.Gly79Arg	missense	Exon 3 of 5	ENSP00000385204.3	Q96FE7-2
	PIK3IP1	ENST00000441972.5	TSL:2	c.235G>A	p.Gly79Arg	missense	Exon 3 of 5	ENSP00000415608.1	Q96FE7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000535 AC: 1 AN: 186930 AF XY: 0.00000986

Gnomad AFR exome AF: 0.00

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: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425912 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706770

African (AFR) AF: 0.00 AC: 0 AN: 32074

American (AMR) AF: 0.00 AC: 0 AN: 40598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 37602

South Asian (SAS) AF: 0.00 AC: 0 AN: 82342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092984

Other (OTH) AF: 0.00 AC: 0 AN: 58848

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000839 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Benign	0.039	D
Sift4G	Uncertain	0.029	D
Polyphen		0.97	D
Vest4		0.27
MutPred		0.84		Gain of glycosylation at P77 (P = 0.0854)
MVP		0.59
MPC		1.0
ClinPred		0.96	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.74
Mutation Taster		=76/24	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: rs746269728; hg19: chr22-31687023;