22-20710913-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.5924-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,599,928 control chromosomes in the GnomAD database, including 3,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (304 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3556 hom.)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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 22-20710913-A-G is Benign according to our data. Variant chr22-20710913-A-G is described in ClinVar as [Benign]. Clinvar id is 1293825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.5924-55T>C		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.5924-55T>C		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10313 AN: 151986 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0807

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0721 AC: 104345 AN: 1447828 Hom.: 3556 Cov.: 28 AF XY: 0.0715 AC XY: 51579 AN XY: 721064

Gnomad4 AFR exome AF: 0.0638

Gnomad4 AMR exome AF: 0.0730

Gnomad4 ASJ exome AF: 0.0290

Gnomad4 EAS exome AF: 0.0661

Gnomad4 SAS exome AF: 0.0661

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.0751

Gnomad4 OTH exome AF: 0.0680

GnomAD4 genome AF: 0.0678 AC: 10317 AN: 152100 Hom.: 304 Cov.: 33 AF XY: 0.0672 AC XY: 5001 AN XY: 74378

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.0807

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0729 Hom.: 36

Asia WGS AF: 0.0600 AC: 209 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	2.4
Dann	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs113356965; hg19: chr22-21065201; COSMIC: COSV55406886; COSMIC: COSV55406886;