chr10-96648752-C-T

Position:

• chr10-96648752-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_152309.3(PIK3AP1):​c.1092G>A​(p.Ala364Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,610,796 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (7 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.10

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]

PIK3AP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-96648752-C-T is Benign according to our data. Variant chr10-96648752-C-T is described in ClinVar as [Benign]. Clinvar id is 474912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00615 (936/152308) while in subpopulation AFR AF= 0.0213 (884/41568). AF 95% confidence interval is 0.0201. There are 7 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 936 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.1092G>A	p.Ala364Ala	synonymous_variant	7/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.1092G>A	p.Ala364Ala	synonymous_variant	7/16		XP_011537550.1
PIK3AP1	XM_005269499.2	c.558G>A	p.Ala186Ala	synonymous_variant	6/16		XP_005269556.1
PIK3AP1	XM_047424566.1	c.558G>A	p.Ala186Ala	synonymous_variant	8/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.1092G>A	p.Ala364Ala	synonymous_variant	7/17	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371110.6	c.558G>A	p.Ala186Ala	synonymous_variant	6/16	2		ENSP00000360151.2
PIK3AP1	ENST00000468783.1	n.738G>A		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 934 AN: 152190 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00169 AC: 419 AN: 247390 Hom.: 4 AF XY: 0.00145 AC XY: 194 AN XY: 133836

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000331

Gnomad SAS exome AF: 0.0000336

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000672

GnomAD4 exome AF: 0.000664 AC: 969 AN: 1458488 Hom.: 7 Cov.: 31 AF XY: 0.000609 AC XY: 442 AN XY: 725552

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.0000586

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000123

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00615 AC: 936 AN: 152308 Hom.: 7 Cov.: 32 AF XY: 0.00603 AC XY: 449 AN XY: 74476

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00288 Hom.: 1

Bravo AF: 0.00659

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Infantile spasms Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

PIK3AP1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.1
DANN	Benign	0.73
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: rs35035564; hg19: chr10-98408509;