10-96718692-C-T

Variant names:

• chr10-96718692-C-T
• rs563654
• NM_152309.3:c.13+1690G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152309.3(PIK3AP1):​c.13+1690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,090 control chromosomes in the GnomAD database, including 3,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3140 hom., cov: 32)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.13+1690G>A		intron_variant	Intron 1 of 16	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_047424566.1	c.-601G>A		splice_region_variant	Exon 2 of 18		XP_047280522.1
PIK3AP1	XM_047424566.1	c.-601G>A		5_prime_UTR_variant	Exon 2 of 18		XP_047280522.1
PIK3AP1	XM_011539248.2	c.13+1690G>A		intron_variant	Intron 1 of 15		XP_011537550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.13+1690G>A		intron_variant	Intron 1 of 16	1	NM_152309.3	ENSP00000339826.5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25060 AN: 151972 Hom.: 3130 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25105 AN: 152090 Hom.: 3140 Cov.: 32 AF XY: 0.165 AC XY: 12295 AN XY: 74362

African (AFR) AF: 0.317 AC: 13122 AN: 41448

American (AMR) AF: 0.284 AC: 4339 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.170 AC: 880 AN: 5172

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4824

European-Finnish (FIN) AF: 0.0899 AC: 952 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0703 AC: 4781 AN: 67996

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.108 Hom.: 3511

Bravo AF: 0.189

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.89
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs563654; hg19: chr10-98478449;