rs74496843

Variant names:

• chr10-96626871-A-G
• rs74496843
• NM_152309.3:c.1506T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_152309.3(PIK3AP1):​c.1506T>C​(p.Asp502Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,174 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (9 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-96626871-A-G is Benign according to our data. Variant chr10-96626871-A-G is described in ClinVar as Benign. ClinVar VariationId is 474915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00671 (1022/152348) while in subpopulation AFR AF = 0.0234 (974/41576). AF 95% confidence interval is 0.0222. There are 17 homozygotes in GnomAd4. There are 494 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1022 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.1506T>C	p.Asp502Asp	synonymous	Exon 10 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.1506T>C	p.Asp502Asp	synonymous	Exon 10 of 17	ENSP00000339826.5	Q6ZUJ8-1
	PIK3AP1	ENST00000371109.3	TSL:1	c.303T>C	p.Asp101Asp	synonymous	Exon 3 of 10	ENSP00000360150.3	Q6ZUJ8-3
	PIK3AP1	ENST00000866991.1		c.1506T>C	p.Asp502Asp	synonymous	Exon 10 of 17	ENSP00000537050.1

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1023 AN: 152230 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

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: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00188 AC: 473 AN: 251286 AF XY: 0.00146

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.00176

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: 0.000489

GnomAD4 exome AF: 0.000722 AC: 1055 AN: 1461826 Hom.: 9 Cov.: 35 AF XY: 0.000644 AC XY: 468 AN XY: 727228

African (AFR) AF: 0.0234 AC: 785 AN: 33478

American (AMR) AF: 0.00190 AC: 85 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

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

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000791 AC: 88 AN: 1111950

Other (OTH) AF: 0.00147 AC: 89 AN: 60394

GnomAD4 genome AF: 0.00671 AC: 1022 AN: 152348 Hom.: 17 Cov.: 32 AF XY: 0.00663 AC XY: 494 AN XY: 74508

African (AFR) AF: 0.0234 AC: 974 AN: 41576

American (AMR) AF: 0.00235 AC: 36 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00348 Hom.: 1

Bravo AF: 0.00742

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile spasms (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs74496843; hg19: chr10-98386628;