rs5760138

Variant names:

• chr22-20708409-G-A
• rs5760138
• NM_058004.4:c.6258-311C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058004.4(PI4KA):​c.6258-311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 150,768 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (292 hom., cov: 28)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.70
• Publications: 2 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 Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-20708409-G-A is Benign according to our data. Variant chr22-20708409-G-A is described in ClinVar as Benign. ClinVar VariationId is 1288189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058004.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	NM_058004.4	MANE Select	c.6258-311C>T		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6192-311C>T		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.6165-311C>T		intron	N/A	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.6258-311C>T		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2631-311C>T		intron	N/A
	PI4KA	ENST00000939414.1		c.6294-311C>T		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9314 AN: 150654 Hom.: 293 Cov.: 28

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.0275

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.0618

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

GnomAD4 genome AF: 0.0618 AC: 9317 AN: 150768 Hom.: 292 Cov.: 28 AF XY: 0.0613 AC XY: 4515 AN XY: 73606

African (AFR) AF: 0.0440 AC: 1803 AN: 40960

American (AMR) AF: 0.0585 AC: 887 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.0275 AC: 95 AN: 3456

East Asian (EAS) AF: 0.0788 AC: 397 AN: 5036

South Asian (SAS) AF: 0.0631 AC: 299 AN: 4742

European-Finnish (FIN) AF: 0.0566 AC: 595 AN: 10510

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0746 AC: 5043 AN: 67600

Other (OTH) AF: 0.0616 AC: 129 AN: 2094

Alfa AF: 0.0672 Hom.: 27

Bravo AF: 0.0611

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.53
PhyloP100		-4.7
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: rs5760138; hg19: chr22-21062697;