chr22-20710099-C-T

Position:

• chr22-20710099-C-T

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.6084-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 693,592 control chromosomes in the GnomAD database, including 9,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1827 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7358 hom.)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368

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=-0.89).
• BP6: Variant 22-20710099-C-T is Benign according to our data. Variant chr22-20710099-C-T is described in ClinVar as [Benign]. Clinvar id is 1297977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6084-102G>A		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6084-102G>A		intron_variant		1	NM_058004.4	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22772 AN: 151990 Hom.: 1828 Cov.: 33

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.157 AC: 85197 AN: 541484 Hom.: 7358 Cov.: 5 AF XY: 0.154 AC XY: 45033 AN XY: 291816

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.0703

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.150 AC: 22770 AN: 152108 Hom.: 1827 Cov.: 33 AF XY: 0.148 AC XY: 11015 AN XY: 74348

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.181

Alfa AF: 0.174 Hom.: 269

Bravo AF: 0.153

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	-0.89
CADD	Benign	7.3
DANN	Benign	0.77

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: rs5760150; hg19: chr22-21064387; COSMIC: COSV55406982; COSMIC: COSV55406982;