22-20709769-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+139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 417,084 control chromosomes in the GnomAD database, including 7,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (35 hom., cov: 20)
  • Exomes 𝑓: 0.080 (7143 hom.)
• 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=-0.88).
• BP6: Variant 22-20709769-C-T is Benign according to our data. Variant chr22-20709769-C-T is described in ClinVar as [Benign]. Clinvar id is 1266351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6173+139G>A		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6173+139G>A		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 2763 AN: 83422 Hom.: 34 Cov.: 20

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0423

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0475

GnomAD4 exome AF: 0.0796 AC: 26551 AN: 333624 Hom.: 7143 AF XY: 0.0759 AC XY: 13698 AN XY: 180482

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.0842

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.0597

Gnomad4 FIN exome AF: 0.0374

Gnomad4 NFE exome AF: 0.0777

Gnomad4 OTH exome AF: 0.0845

GnomAD4 genome AF: 0.0332 AC: 2769 AN: 83460 Hom.: 35 Cov.: 20 AF XY: 0.0342 AC XY: 1399 AN XY: 40954

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.306 Hom.: 760

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.26
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28718601; hg19: chr22-21064057; COSMIC: COSV55421443; COSMIC: COSV55421443;