rs165793

Variant names:

• chr22-20793005-A-G
• rs165793
• NM_058004.4:c.2328+188T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-20793005-A-G
• chr22-20793005-A-C
• chr22-20793005-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058004.4(PI4KA):​c.2328+188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,056 control chromosomes in the GnomAD database, including 48,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.80 (48466 hom., cov: 31)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.72
• Publications: 12 publications found

Genes affected

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

PI4KA Gene-Disease associations (from GenCC):

• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 22-20793005-A-G is Benign according to our data. Variant chr22-20793005-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058004.4. 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
	PI4KA	NM_058004.4	MANE Select	c.2328+188T>C		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.2262+188T>C		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.2328+188T>C		intron	N/A	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.2328+188T>C		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000939414.1		c.2328+188T>C		intron	N/A	ENSP00000609473.1
	PI4KA	ENST00000939412.1		c.2328+188T>C		intron	N/A	ENSP00000609471.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120838 AN: 151938 Hom.: 48428 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.797

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.795 AC: 120933 AN: 152056 Hom.: 48466 Cov.: 31 AF XY: 0.787 AC XY: 58527 AN XY: 74332

African (AFR) AF: 0.871 AC: 36144 AN: 41478

American (AMR) AF: 0.742 AC: 11335 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2539 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3281 AN: 5170

South Asian (SAS) AF: 0.729 AC: 3508 AN: 4812

European-Finnish (FIN) AF: 0.685 AC: 7243 AN: 10572

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54232 AN: 67966

Other (OTH) AF: 0.797 AC: 1680 AN: 2108

Alfa AF: 0.792 Hom.: 124552

Bravo AF: 0.804

Asia WGS AF: 0.688 AC: 2390 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.55
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs165793; hg19: chr22-21147293;