chr22-20708409-G-A

Position:

• chr22-20708409-G-A

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.6258-311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 150,768 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (292 hom., cov: 28)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.70

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=-0.91).
• BP6: Variant 22-20708409-G-A is Benign according to our data. Variant chr22-20708409-G-A is described in ClinVar as [Benign]. Clinvar id is 1288189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6258-311C>T		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6258-311C>T		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9314 AN: 150654 Hom.: 293 Cov.: 28

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.0275

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.0618

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

GnomAD4 genome AF: 0.0618 AC: 9317 AN: 150768 Hom.: 292 Cov.: 28 AF XY: 0.0613 AC XY: 4515 AN XY: 73606

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.0585

Gnomad4 ASJ AF: 0.0275

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.0631

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.0746

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0684 Hom.: 27

Bravo AF: 0.0611

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	-0.91
CADD	Benign	0.70
DANN	Benign	0.53

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: rs5760138; hg19: chr22-21062697;