22-20745009-T-C

Position:

• chr22-20745009-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000255882.11(PI4KA):​c.3364-289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,016 control chromosomes in the GnomAD database, including 13,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13235 hom., cov: 31)
• Consequence: PI4KA ENST00000255882.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.610

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=-0.9).
• BP6: Variant 22-20745009-T-C is Benign according to our data. Variant chr22-20745009-T-C is described in ClinVar as [Benign]. Clinvar id is 1231695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4KA	NM_058004.4	c.3364-289A>G		intron_variant		ENST00000255882.11	NP_477352.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI4KA	ENST00000255882.11	c.3364-289A>G		intron_variant		1	NM_058004.4	ENSP00000255882	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62261 AN: 151898 Hom.: 13214 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.410 AC: 62322 AN: 152016 Hom.: 13235 Cov.: 31 AF XY: 0.404 AC XY: 30020 AN XY: 74282

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.441

Alfa AF: 0.361 Hom.: 5684

Bravo AF: 0.436

Asia WGS AF: 0.412 AC: 1431 AN: 3478

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	-0.90
CADD	Benign	1.9
DANN	Benign	0.36

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: rs2072513; hg19: chr22-21099297;