10-96602303-C-T

Variant names:

• chr10-96602303-C-T
• rs145459703
• NM_152309.3:c.2337G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152309.3(PIK3AP1):​c.2337G>A​(p.Val779Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,605,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: PIK3AP1 NM_152309.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206
• 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]

LOC105378443 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-96602303-C-T is Benign according to our data. Variant chr10-96602303-C-T is described in ClinVar as Benign. ClinVar VariationId is 474927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 212 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.2337G>A	p.Val779Val	synonymous	Exon 16 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.2337G>A	p.Val779Val	synonymous	Exon 16 of 17	ENSP00000339826.5	Q6ZUJ8-1
	PIK3AP1	ENST00000371109.3	TSL:1	c.1134G>A	p.Val378Val	synonymous	Exon 9 of 10	ENSP00000360150.3	Q6ZUJ8-3
	PIK3AP1	ENST00000866991.1		c.2430G>A	p.Val810Val	synonymous	Exon 16 of 17	ENSP00000537050.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000366 AC: 89 AN: 242860 AF XY: 0.000258

Gnomad AFR exome AF: 0.00519

Gnomad AMR exome AF: 0.000158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000137 AC: 199 AN: 1452966 Hom.: 0 Cov.: 30 AF XY: 0.000129 AC XY: 93 AN XY: 722942

African (AFR) AF: 0.00497 AC: 163 AN: 32768

American (AMR) AF: 0.000286 AC: 12 AN: 41890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25780

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39580

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109044

Other (OTH) AF: 0.000333 AC: 20 AN: 60002

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74462

African (AFR) AF: 0.00493 AC: 205 AN: 41556

American (AMR) AF: 0.000131 AC: 2 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000428 Hom.: 0

Bravo AF: 0.00145

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.51
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		-0.21

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: rs145459703; hg19: chr10-98362060;