10-96602288-G-C

Variant names:

• chr10-96602288-G-C
• rs1390796047
• NM_152309.3:c.2352C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152309.3(PIK3AP1):​c.2352C>G​(p.Ala784Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A784A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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]

LOC105378443 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.2352C>G	p.Ala784Ala	synonymous_variant	Exon 16 of 17	ENST00000339364.10	NP_689522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.2352C>G	p.Ala784Ala	synonymous_variant	Exon 16 of 17	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371109.3	c.1149C>G	p.Ala383Ala	synonymous_variant	Exon 9 of 10	1		ENSP00000360150.3
PIK3AP1	ENST00000371110.6	c.1818C>G	p.Ala606Ala	synonymous_variant	Exon 15 of 16	2		ENSP00000360151.2
PIK3AP1	ENST00000467625.5	n.549C>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.5
DANN	Benign	0.45
PhyloP100		-0.14

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: rs1390796047; hg19: chr10-98362045;