Variant rs796052191 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

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

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.18

Variant links:

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 links:

PI4KA (HGNC:):

PI4KA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PI4KA. . Gene score misZ 3.5271 (greater than the threshold 3.09). Trascript score misZ 4.6291 (greater than threshold 3.09). GenCC has associacion of gene with polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4KA	NM_058004.4 linkuse as main transcript	c.421G>A	p.Asp141Asn	missense_variant	4/55	ENST00000255882.11	NP_477352.3	P42356-1Q4LE69B4DYG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PI4KA	ENST00000255882.11 linkuse as main transcript	c.421G>A	p.Asp141Asn	missense_variant	4/55	1	NM_058004.4	ENSP00000255882.6	P42356-1
PI4KA	ENST00000449120.1 linkuse as main transcript	c.247G>A	p.Asp83Asn	missense_variant	4/4	4		ENSP00000402437.1	C9JLI1
PI4KA	ENST00000485963.5 linkuse as main transcript	n.508G>A		non_coding_transcript_exon_variant	4/17	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Long QT syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.80

D;D

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.47

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.7

.;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.0030

D;D

Vest4

0.91

MutPred

0.61

.;Gain of helix (P = 0.0696);

MVP

0.67

MPC

0.93

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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