22-20793005-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -2.72

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1222163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.2328+188T>C		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.2328+188T>C		intron_variant		1	NM_058004.4	P1
PI4KA	ENST00000466162.5	n.91+188T>C		intron_variant, non_coding_transcript_variant		4
PI4KA	ENST00000484220.1	n.64+188T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.797

Alfa AF: 0.790 Hom.: 84539

Bravo AF: 0.804

Asia WGS AF: 0.688 AC: 2390 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.20
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs165793; hg19: chr22-21147293;