10-96648752-C-T

Variant names:

• chr10-96648752-C-T
• rs35035564
• NM_152309.3:c.1092G>A

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. A364A) has been classified as Likely 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
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 936 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.1092G>A	p.Ala364Ala	synonymous	Exon 7 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.1092G>A	p.Ala364Ala	synonymous	Exon 7 of 17	ENSP00000339826.5	Q6ZUJ8-1
	PIK3AP1	ENST00000866991.1		c.1092G>A	p.Ala364Ala	synonymous	Exon 7 of 17	ENSP00000537050.1
	PIK3AP1	ENST00000866992.1		c.1092G>A	p.Ala364Ala	synonymous	Exon 7 of 16	ENSP00000537051.1

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

GnomAD2 exomes AF: 0.00169 AC: 419 AN: 247390 AF XY: 0.00145

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 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

African (AFR) AF: 0.0199 AC: 665 AN: 33362

American (AMR) AF: 0.00136 AC: 60 AN: 44028

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26090

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39404

South Asian (SAS) AF: 0.0000586 AC: 5 AN: 85378

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53394

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1110788

Other (OTH) AF: 0.00139 AC: 84 AN: 60282

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

African (AFR) AF: 0.0213 AC: 884 AN: 41568

American (AMR) AF: 0.00163 AC: 25 AN: 15304

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

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00696 Hom.: 4

Bravo AF: 0.00659

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile spasms (1)
-	-	1	not provided (1)
-	-	1	PIK3AP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs35035564; hg19: chr10-98408509;