chr22-20709687-A-AAC

Variant names:

• chr22-20709687-A-AAC
• rs373609759
• NM_058004.4:c.6173+220_6173+221insGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_058004.4(PI4KA):​c.6173+220_6173+221insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 0)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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.6173+220_6173+221insGT		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6107+220_6107+221insGT		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.6080+220_6080+221insGT		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.6173+220_6173+221insGT		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2546+220_2546+221insGT		intron	N/A
	PI4KA	ENST00000939414.1		c.6209+220_6209+221insGT		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 2 AN: 100412 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000406

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000199 AC: 2 AN: 100412 Hom.: 0 Cov.: 0 AF XY: 0.0000411 AC XY: 2 AN XY: 48642

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22862

American (AMR) AF: 0.00 AC: 0 AN: 9248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2538

East Asian (EAS) AF: 0.00 AC: 0 AN: 3368

South Asian (SAS) AF: 0.00 AC: 0 AN: 3060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000406 AC: 2 AN: 49288

Other (OTH) AF: 0.00 AC: 0 AN: 1296

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs373609759; hg19: chr22-21063975;