chr22-31283281-C-T

Variant names:

• chr22-31283281-C-T
• NM_052880.5:c.595G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052880.5(PIK3IP1):​c.595G>A​(p.Asp199Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIK3IP1 NM_052880.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16732588).

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.595G>A	p.Asp199Asn	missense	Exon 6 of 6	NP_443112.2	Q96FE7-1
	PIK3IP1	NM_001135911.1		c.516G>A	p.Arg172Arg	synonymous	Exon 5 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.595G>A	p.Asp199Asn	missense	Exon 6 of 6	ENSP00000215912.4	Q96FE7-1
	PIK3IP1	ENST00000885856.1		c.358G>A	p.Asp120Asn	missense	Exon 4 of 4	ENSP00000555915.1
	PIK3IP1	ENST00000441972.5	TSL:2	c.516G>A	p.Arg172Arg	synonymous	Exon 5 of 5	ENSP00000415608.1	Q96FE7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.83	T
PhyloP100		4.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.13	B
Vest4		0.22
MutPred		0.30		Loss of ubiquitination at K201 (P = 0.0273)
MVP		0.75
MPC		0.88
ClinPred		0.99	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.45
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

hg19: chr22-31679267;