22-20707980-G-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.*67C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,356,082 control chromosomes in the GnomAD database, including 3,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (306 hom., cov: 30)
  • Exomes 𝑓: 0.072 (3250 hom.)
• Consequence: PI4KA NM_058004.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

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 22-20707980-G-T is Benign according to our data. Variant chr22-20707980-G-T is described in ClinVar as [Benign]. Clinvar id is 1262196.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.*67C>A		3_prime_UTR_variant	55/55	ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.*67C>A		3_prime_UTR_variant	55/55	1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9577 AN: 152130 Hom.: 307 Cov.: 30

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0720 AC: 86618 AN: 1203834 Hom.: 3250 Cov.: 17 AF XY: 0.0714 AC XY: 43675 AN XY: 611724

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.0725

Gnomad4 ASJ exome AF: 0.0293

Gnomad4 EAS exome AF: 0.0662

Gnomad4 SAS exome AF: 0.0664

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0674

GnomAD4 genome AF: 0.0629 AC: 9581 AN: 152248 Hom.: 306 Cov.: 30 AF XY: 0.0624 AC XY: 4646 AN XY: 74446

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.0785

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0758

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0562 Hom.: 106

Bravo AF: 0.0612

Asia WGS AF: 0.0600 AC: 208 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	0.039
Dann	Benign	0.53
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: rs13471; hg19: chr22-21062268; COSMIC: COSV55403608; COSMIC: COSV55403608;