NM_152309.3:c.554G>T

Variant names:

• chr10-96656811-C-A
• rs1364487885
• NM_152309.3:c.554G>T

Variant summary

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

The NM_152309.3(PIK3AP1):​c.554G>T​(p.Arg185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R185C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 3 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152309.3. 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
	PIK3AP1	NM_152309.3	MANE Select	c.554G>T	p.Arg185Leu	missense	Exon 3 of 17	NP_689522.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3AP1	ENST00000339364.10	TSL:1 MANE Select	c.554G>T	p.Arg185Leu	missense	Exon 3 of 17	ENSP00000339826.5	Q6ZUJ8-1
	PIK3AP1	ENST00000866991.1		c.554G>T	p.Arg185Leu	missense	Exon 3 of 17	ENSP00000537050.1
	PIK3AP1	ENST00000866992.1		c.554G>T	p.Arg185Leu	missense	Exon 3 of 16	ENSP00000537051.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461726 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.4
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.97	D
Vest4		0.70
MutPred		0.48		Loss of solvent accessibility (P = 0.0299)
MVP		0.33
MPC		1.6
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.71
gMVP		0.81
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

dbSNP: rs1364487885; hg19: chr10-98416568;