chr22-20709832-G-A

Position:

• chr22-20709832-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058004.4(PI4KA):​c.6173+76C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 853,092 control chromosomes in the GnomAD database, including 2,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (441 hom., cov: 27)
  • Exomes 𝑓: 0.068 (1722 hom.)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.599

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-20709832-G-A is Benign according to our data. Variant chr22-20709832-G-A is described in ClinVar as [Benign]. Clinvar id is 1182068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6173+76C>T		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6173+76C>T		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 10837 AN: 145600 Hom.: 443 Cov.: 27

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.0641

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0419

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0719

GnomAD4 exome AF: 0.0678 AC: 47986 AN: 707380 Hom.: 1722 AF XY: 0.0679 AC XY: 25818 AN XY: 380030

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.0741

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.0703

Gnomad4 FIN exome AF: 0.0548

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.0744 AC: 10846 AN: 145712 Hom.: 441 Cov.: 27 AF XY: 0.0743 AC XY: 5271 AN XY: 70958

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0775 Hom.: 50

Bravo AF: 0.0731

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.88
CADD	Benign	2.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs146546335; hg19: chr22-21064120;