rs145525421

Variant names:

• chr10-96628457-A-T
• rs145525421
• NM_152309.3:c.1412T>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_152309.3(PIK3AP1):​c.1412T>A​(p.Ile471Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00055 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000090 (1 hom.)
• Consequence: PIK3AP1 NM_152309.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0690
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008630097).
• BP6: Variant 10-96628457-A-T is Benign according to our data. Variant chr10-96628457-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 541753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 84 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152309.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3AP1	NM_152309.3	MANE Select	c.1412T>A	p.Ile471Asn	missense	Exon 9 of 17	NP_689522.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3AP1	ENST00000339364.10	TSL:1 MANE Select	c.1412T>A	p.Ile471Asn	missense	Exon 9 of 17	ENSP00000339826.5	Q6ZUJ8-1
	PIK3AP1	ENST00000371109.3	TSL:1	c.209T>A	p.Ile70Asn	missense	Exon 2 of 10	ENSP00000360150.3	Q6ZUJ8-3
	PIK3AP1	ENST00000866991.1		c.1412T>A	p.Ile471Asn	missense	Exon 9 of 17	ENSP00000537050.1

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152112 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251244 AF XY: 0.000125

Gnomad AFR exome AF: 0.00221

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000896 AC: 131 AN: 1461296 Hom.: 1 Cov.: 30 AF XY: 0.0000757 AC XY: 55 AN XY: 726992

African (AFR) AF: 0.00269 AC: 90 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111482

Other (OTH) AF: 0.000182 AC: 11 AN: 60374

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152230 Hom.: 1 Cov.: 31 AF XY: 0.000538 AC XY: 40 AN XY: 74416

African (AFR) AF: 0.00195 AC: 81 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000631

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000189 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile spasms (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.75
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.069
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift	Benign	0.031	D
Sift4G	Benign	0.23	T
Polyphen		0.37	B
Vest4		0.17
MVP		0.12
MPC		1.0
ClinPred		0.015	T
GERP RS		0.40
Varity_R		0.048
gMVP		0.21
Mutation Taster		=83/17	polymorphism

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: rs145525421; hg19: chr10-98388214;