rs34642975

Variant names:

• chr10-96651261-T-A
• NM_152309.3:c.975A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-96651261-T-A
• chr10-96651261-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_152309.3(PIK3AP1):​c.975A>T​(p.Glu325Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06947163).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.975A>T	p.Glu325Asp	missense_variant	Exon 6 of 17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.975A>T	p.Glu325Asp	missense_variant	Exon 6 of 16		XP_011537550.1
PIK3AP1	XM_005269499.2	c.441A>T	p.Glu147Asp	missense_variant	Exon 5 of 16		XP_005269556.1
PIK3AP1	XM_047424566.1	c.441A>T	p.Glu147Asp	missense_variant	Exon 7 of 18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.975A>T	p.Glu325Asp	missense_variant	Exon 6 of 17	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371110.6	c.441A>T	p.Glu147Asp	missense_variant	Exon 5 of 16	2		ENSP00000360151.2
PIK3AP1	ENST00000468783.1	n.621A>T		non_coding_transcript_exon_variant	Exon 5 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461840 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.082	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.75	N;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.044
Sift	Benign	0.53	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0010	B;.
Vest4		0.21
MutPred		0.30		Gain of helix (P = 0.0082);.;
MVP		0.16
MPC		0.51
ClinPred		0.076	T
GERP RS		-2.5
Varity_R		0.056
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-98411018;