22-20707880-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_058004.4(PI4KA):c.*167G>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 0.0389 in 744,930 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (100 hom., cov: 30)
  • Exomes 𝑓: 0.040 (595 hom.)
• Consequence: PI4KA NM_058004.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.411

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=-0.83).
• BP6: Variant 22-20707880-C-T is Benign according to our data. Variant chr22-20707880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1320583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0333 (5072/152328) while in subpopulation NFE AF= 0.05 (3403/68028). AF 95% confidence interval is 0.0486. There are 100 homozygotes in gnomad4. There are 2475 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.*167G>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.*167G>A		3_prime_UTR_variant	55/55	1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5074 AN: 152210 Hom.: 100 Cov.: 30

Gnomad AFR AF: 0.00914

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0403 AC: 23894 AN: 592602 Hom.: 595 Cov.: 5 AF XY: 0.0403 AC XY: 12975 AN XY: 321756

Gnomad4 AFR exome AF: 0.00898

Gnomad4 AMR exome AF: 0.0232

Gnomad4 ASJ exome AF: 0.0325

Gnomad4 EAS exome AF: 0.000197

Gnomad4 SAS exome AF: 0.0314

Gnomad4 FIN exome AF: 0.0415

Gnomad4 NFE exome AF: 0.0497

Gnomad4 OTH exome AF: 0.0440

GnomAD4 genome AF: 0.0333 AC: 5072 AN: 152328 Hom.: 100 Cov.: 30 AF XY: 0.0332 AC XY: 2475 AN XY: 74494

Gnomad4 AFR AF: 0.00912

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0447 Hom.: 68

Bravo AF: 0.0324

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.55

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: rs1058552; hg19: chr22-21062168;