rs374819025

Positions:

• chr10-96648830-G-A
• chr10-96648830-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152309.3(PIK3AP1):​c.1014C>T​(p.Thr338=) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.1014C>T	p.Thr338=	synonymous_variant	7/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.1014C>T	p.Thr338=	synonymous_variant	7/16		XP_011537550.1
PIK3AP1	XM_005269499.2	c.480C>T	p.Thr160=	synonymous_variant	6/16		XP_005269556.1
PIK3AP1	XM_047424566.1	c.480C>T	p.Thr160=	synonymous_variant	8/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1014C>T	p.Thr338=	synonymous_variant	7/17	1	NM_152309.3	ENSP00000339826	P1
PIK3AP1	ENST00000371110.6	c.480C>T	p.Thr160=	synonymous_variant	6/16	2		ENSP00000360151
PIK3AP1	ENST00000468783.1	n.660C>T		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000448 AC: 1 AN: 223358 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 121522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000953

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.4
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs374819025; hg19: chr10-98408587;