Variant chr22-20709982-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_058004.4(PI4KA):c.6099G>A(p.Ala2033=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,613,212 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 29)

Exomes 𝑓: 0.0039 ( 9 hom. )

Consequence

PI4KA
NM_058004.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 22-20709982-C-T is Benign according to our data. Variant chr22-20709982-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20709982-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00274 (417/152310) while in subpopulation NFE AF= 0.00526 (358/68032). AF 95% confidence interval is 0.00481. There are 4 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4 linkuse as main transcript	c.6099G>A	p.Ala2033=	synonymous_variant	53/55	ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11 linkuse as main transcript	c.6099G>A	p.Ala2033=	synonymous_variant	53/55	1	NM_058004.4	P1	P42356-1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00225

AC:

563

AN:

250714

Hom.:

AF XY:

0.00245

AC XY:

333

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00415

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00388

AC:

5666

AN:

1460902

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

2857

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.000956

Gnomad4 NFE exome

AF:

0.00480

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152310

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00475

Hom.:

Bravo

AF:

0.00246

EpiCase

AF:

0.00453

EpiControl

AF:

0.00350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	PI4KA: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.7

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Other links and lift over