NM_052880.5:c.181G>T

Variant names:

• chr22-31291186-C-A
• rs200641882
• NM_052880.5:c.181G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052880.5(PIK3IP1):​c.181G>T​(p.Val61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V61M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PIK3IP1 NM_052880.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05353138).

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.181G>T	p.Val61Leu	missense	Exon 2 of 6	NP_443112.2	Q96FE7-1
	PIK3IP1	NM_001135911.1		c.181G>T	p.Val61Leu	missense	Exon 2 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.181G>T	p.Val61Leu	missense	Exon 2 of 6	ENSP00000215912.4	Q96FE7-1
	PIK3IP1	ENST00000402249.7	TSL:1	c.181G>T	p.Val61Leu	missense	Exon 2 of 5	ENSP00000385204.3	Q96FE7-2
	PIK3IP1	ENST00000441972.5	TSL:2	c.181G>T	p.Val61Leu	missense	Exon 2 of 5	ENSP00000415608.1	Q96FE7-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000701 AC: 1 AN: 142750 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1394330 Hom.: 0 Cov.: 38 AF XY: 0.00000145 AC XY: 1 AN XY: 687716

African (AFR) AF: 0.00 AC: 0 AN: 30960

American (AMR) AF: 0.00 AC: 0 AN: 35346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24964

East Asian (EAS) AF: 0.00 AC: 0 AN: 35414

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077274

Other (OTH) AF: 0.00 AC: 0 AN: 57792

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.9
DANN	Benign	0.68
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
PhyloP100		-0.39
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.048
Sift	Benign	0.66	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.39		Loss of catalytic residue at V61 (P = 0.1017)
MVP		0.26
MPC		0.27
ClinPred		0.017	T
GERP RS		1.6
Varity_R		0.046
gMVP		0.46
Mutation Taster		=91/9	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: rs200641882; hg19: chr22-31687172;