22-20709708-C-T

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.6173+200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (5574 hom., cov: 16)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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=-0.94).
• BP6: Variant 22-20709708-C-T is Benign according to our data. Variant chr22-20709708-C-T is described in ClinVar as [Benign]. Clinvar id is 1286373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6173+200G>A		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6173+200G>A		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 30052 AN: 81308 Hom.: 5564 Cov.: 16

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.336

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.370 AC: 30098 AN: 81398 Hom.: 5574 Cov.: 16 AF XY: 0.362 AC XY: 14412 AN XY: 39834

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.382

Alfa AF: 0.455 Hom.: 1506

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

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.73
Dann	Benign	0.30

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: rs435091; hg19: chr22-21063996; COSMIC: COSV55425809; COSMIC: COSV55425809;