rs796052191

Variant names:

• chr22-20824361-C-T
• rs796052191
• NM_058004.4:c.421G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058004.4(PI4KA):​c.421G>A​(p.Asp141Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PI4KA NM_058004.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.18
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.421G>A	p.Asp141Asn	missense	Exon 4 of 55	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.421G>A	p.Asp141Asn	missense	Exon 4 of 54	NP_001349792.1
	PI4KA	NM_001362862.2		c.421G>A	p.Asp141Asn	missense	Exon 4 of 54	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.421G>A	p.Asp141Asn	missense	Exon 4 of 55	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000939414.1		c.421G>A	p.Asp141Asn	missense	Exon 4 of 56	ENSP00000609473.1
	PI4KA	ENST00000939412.1		c.421G>A	p.Asp141Asn	missense	Exon 4 of 55	ENSP00000609471.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461466 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.47	T
PhyloP100		7.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Vest4		0.91
MutPred		0.61		Gain of helix (P = 0.0696)
MVP		0.67
MPC		0.93
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.69
Mutation Taster		=10/90	disease causing

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: rs796052191; hg19: chr22-21178649;