rs765634361

chr10-96602367-C-Achr10-96602367-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152309.3(PIK3AP1):c.2273G>T(p.Arg758Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R758C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105378443 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15164751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.2273G>T	p.Arg758Leu	missense_variant	16/17	ENST00000339364.10
LOC105378443	XR_946220.4	n.1447-5309C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.2273G>T	p.Arg758Leu	missense_variant	16/17	1	NM_152309.3	P1
PIK3AP1	ENST00000371109.3	c.1070G>T	p.Arg357Leu	missense_variant	9/10	1
PIK3AP1	ENST00000371110.6	c.1739G>T	p.Arg580Leu	missense_variant	15/16	2
PIK3AP1	ENST00000467625.5	n.470G>T		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.043
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.85	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.092	T;T;D
Sift4G	Benign	0.67	T;T;T
Polyphen		0.63	P;.;P
Vest4		0.32
MutPred		0.21		Loss of loop (P = 0.0804);.;.;
MVP		0.27
MPC		0.99
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765634361; hg19: chr10-98362124;