rs111902593

chr10-96604056-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152309.3(PIK3AP1):c.2171-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,581,012 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (111 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (122 hom.)
• Consequence: PIK3AP1 NM_152309.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.125

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-96604056-G-A is Benign according to our data. Variant chr10-96604056-G-A is described in ClinVar as [Benign]. Clinvar id is 474922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.2171-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000339364.10
LOC105378443	XR_946220.4	n.1447-3620G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.2171-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152309.3	P1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3176 AN: 151854 Hom.: 111 Cov.: 31

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00911

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00590 AC: 1299 AN: 220016 Hom.: 39 AF XY: 0.00459 AC XY: 542 AN XY: 118138

Gnomad AFR exome AF: 0.0754

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000301

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000512

Gnomad OTH exome AF: 0.00438

GnomAD4 exome AF: 0.00265 AC: 3786 AN: 1429040 Hom.: 122 Cov.: 29 AF XY: 0.00237 AC XY: 1682 AN XY: 710258

Gnomad4 AFR exome AF: 0.0776

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00790

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000419

Gnomad4 OTH exome AF: 0.00634

GnomAD4 genome AF: 0.0210 AC: 3184 AN: 151972 Hom.: 111 Cov.: 31 AF XY: 0.0201 AC XY: 1492 AN XY: 74284

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.00910

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0109 Hom.: 16

Bravo AF: 0.0242

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile spasms Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.050		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: rs111902593; hg19: chr10-98363813;