NM_152309.3:c.2076A>G

Variant names:

• chr10-96609806-T-C
• rs141067860
• NM_152309.3:c.2076A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152309.3(PIK3AP1):​c.2076A>G​(p.Gly692Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,614,066 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (6 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.604
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-96609806-T-C is Benign according to our data. Variant chr10-96609806-T-C is described in ClinVar as Benign. ClinVar VariationId is 474919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.604 with no splicing effect.
• BS2: High AC in GnomAd4 at 248 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.2076A>G	p.Gly692Gly	synonymous	Exon 14 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.2076A>G	p.Gly692Gly	synonymous	Exon 14 of 17	ENSP00000339826.5
	PIK3AP1	ENST00000371109.3	TSL:1	c.873A>G	p.Gly291Gly	synonymous	Exon 7 of 10	ENSP00000360150.3
	PIK3AP1	ENST00000866991.1		c.2076A>G	p.Gly692Gly	synonymous	Exon 14 of 17	ENSP00000537050.1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152138 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00149 AC: 374 AN: 251372 AF XY: 0.00162

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00210 AC: 3074 AN: 1461810 Hom.: 6 Cov.: 31 AF XY: 0.00207 AC XY: 1507 AN XY: 727218

African (AFR) AF: 0.000149 AC: 5 AN: 33476

American (AMR) AF: 0.000470 AC: 21 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000904 AC: 78 AN: 86254

European-Finnish (FIN) AF: 0.00155 AC: 83 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00248 AC: 2754 AN: 1111946

Other (OTH) AF: 0.00157 AC: 95 AN: 60394

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152256 Hom.: 2 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74450

African (AFR) AF: 0.000457 AC: 19 AN: 41538

American (AMR) AF: 0.000850 AC: 13 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.00115

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00207

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile spasms (1)
-	-	1	PIK3AP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141067860; hg19: chr10-98369563;