rs165789

Variant names:

• chr22-20817304-G-A
• rs165789
• NM_058004.4:c.856+1179C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058004.4(PI4KA):​c.856+1179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,874 control chromosomes in the GnomAD database, including 18,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18575 hom., cov: 31)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 5 publications found

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]

PI4KA Gene-Disease associations (from GenCC):

• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4KA	NM_058004.4	c.856+1179C>T		intron_variant	Intron 7 of 54	ENST00000255882.11	NP_477352.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4KA	ENST00000255882.11	c.856+1179C>T		intron_variant	Intron 7 of 54	1	NM_058004.4	ENSP00000255882.6
PI4KA	ENST00000485963.5	n.943+1179C>T		intron_variant	Intron 7 of 16	2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74013 AN: 151756 Hom.: 18555 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74084 AN: 151874 Hom.: 18575 Cov.: 31 AF XY: 0.481 AC XY: 35733 AN XY: 74224

African (AFR) AF: 0.586 AC: 24271 AN: 41384

American (AMR) AF: 0.537 AC: 8190 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2721 AN: 5170

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4814

European-Finnish (FIN) AF: 0.288 AC: 3042 AN: 10546

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.449 AC: 30466 AN: 67922

Other (OTH) AF: 0.513 AC: 1083 AN: 2110

Alfa AF: 0.471 Hom.: 2114

Bravo AF: 0.512

Asia WGS AF: 0.477 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.48
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs165789; hg19: chr22-21171592;