rs147376017

chr10-96602389-C-Achr10-96602389-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152309.3(PIK3AP1):c.2251G>T(p.Val751Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,610,832 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000092 (3 hom.)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.370

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005790204).
• BP6: Variant 10-96602389-C-A is Benign according to our data. Variant chr10-96602389-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 474925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.2251G>T	p.Val751Phe	missense_variant	16/17	ENST00000339364.10
LOC105378443	XR_946220.4	n.1447-5287C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.2251G>T	p.Val751Phe	missense_variant	16/17	1	NM_152309.3	P1
PIK3AP1	ENST00000371109.3	c.1048G>T	p.Val350Phe	missense_variant	9/10	1
PIK3AP1	ENST00000371110.6	c.1717G>T	p.Val573Phe	missense_variant	15/16	2
PIK3AP1	ENST00000467625.5	n.448G>T		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.000159 AC: 40 AN: 251254 Hom.: 0 AF XY: 0.000110 AC XY: 15 AN XY: 135808

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.000145

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000919 AC: 134 AN: 1458568 Hom.: 3 Cov.: 30 AF XY: 0.0000937 AC XY: 68 AN XY: 725710

Gnomad4 AFR exome AF: 0.00275

Gnomad4 AMR exome AF: 0.000112

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: 0.00000361

Gnomad4 OTH exome AF: 0.000548

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74448

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.0000755 Hom.: 0

Bravo AF: 0.000676

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile spasms Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	19
Dann	Benign	0.95
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N;.;.
MutationTaster	Benign	0.93	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.47	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.13
MVP		0.13
MPC		0.72
ClinPred		0.010	T
GERP RS		2.1
Varity_R		0.042
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147376017; hg19: chr10-98362146;