10-96651536-G-A

Position:

• chr10-96651536-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_152309.3(PIK3AP1):​c.828C>T​(p.Ala276Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,614,100 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.029 (780 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.753

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-96651536-G-A is Benign according to our data. Variant chr10-96651536-G-A is described in ClinVar as [Benign]. Clinvar id is 474932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-96651536-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.753 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0236 (3600/152264) while in subpopulation NFE AF= 0.0343 (2332/68020). AF 95% confidence interval is 0.0331. There are 62 homozygotes in gnomad4. There are 1755 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3600 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.828C>T	p.Ala276Ala	synonymous_variant	5/17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.828C>T	p.Ala276Ala	synonymous_variant	5/16		XP_011537550.1
PIK3AP1	XM_005269499.2	c.294C>T	p.Ala98Ala	synonymous_variant	4/16		XP_005269556.1
PIK3AP1	XM_047424566.1	c.294C>T	p.Ala98Ala	synonymous_variant	6/18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.828C>T	p.Ala276Ala	synonymous_variant	5/17	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371110.6	c.294C>T	p.Ala98Ala	synonymous_variant	4/16	2		ENSP00000360151.2
PIK3AP1	ENST00000468783.1	n.474C>T		non_coding_transcript_exon_variant	4/8	5

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3603 AN: 152146 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00541

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0256 AC: 6448 AN: 251400 Hom.: 113 AF XY: 0.0257 AC XY: 3495 AN XY: 135874

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.0307

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00568

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0300

GnomAD4 exome AF: 0.0295 AC: 43110 AN: 1461836 Hom.: 780 Cov.: 32 AF XY: 0.0291 AC XY: 21159 AN XY: 727208

Gnomad4 AFR exome AF: 0.00421

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0295

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00618

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0332

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0236 AC: 3600 AN: 152264 Hom.: 62 Cov.: 32 AF XY: 0.0236 AC XY: 1755 AN XY: 74438

Gnomad4 AFR AF: 0.00539

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0329 Hom.: 150

Bravo AF: 0.0227

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0327

EpiControl AF: 0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 30, 2024

- -

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	-0.41
CADD	Benign	5.6
DANN	Benign	0.66

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: rs35668691; hg19: chr10-98411293;