rs185079778

Variant names:

• chr10-96626878-T-A
• rs185079778
• NM_152309.3:c.1499A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-96626878-T-A
• chr10-96626878-T-C

Variant summary

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

The NM_152309.3(PIK3AP1):​c.1499A>T​(p.Glu500Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E500G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

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]

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=0.16666391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.1499A>T	p.Glu500Val	missense_variant	Exon 10 of 17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.1499A>T	p.Glu500Val	missense_variant	Exon 10 of 16		XP_011537550.1
PIK3AP1	XM_005269499.2	c.965A>T	p.Glu322Val	missense_variant	Exon 9 of 16		XP_005269556.1
PIK3AP1	XM_047424566.1	c.965A>T	p.Glu322Val	missense_variant	Exon 11 of 18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1499A>T	p.Glu500Val	missense_variant	Exon 10 of 17	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371109.3	c.296A>T	p.Glu99Val	missense_variant	Exon 3 of 10	1		ENSP00000360150.3
PIK3AP1	ENST00000371110.6	c.965A>T	p.Glu322Val	missense_variant	Exon 9 of 16	2		ENSP00000360151.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461816 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.029
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.078	B;.;B
Vest4		0.22
MutPred		0.36		Loss of solvent accessibility (P = 0.0062);.;.;
MVP		0.24
MPC		0.63
ClinPred		0.72	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.46
Mutation Taster		=62/38	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: rs185079778; hg19: chr10-98386635;