NM_058004.4:c.6173+220_6173+221insAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_058004.4(PI4KA):​c.6173+220_6173+221insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (3644 hom., cov: 0)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 22-20709687-A-AAT is Benign according to our data. Variant chr22-20709687-A-AAT is described in ClinVar as Benign. ClinVar VariationId is 1264873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 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.6173+220_6173+221insAT		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6107+220_6107+221insAT		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.6080+220_6080+221insAT		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+221insAT		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2546+220_2546+221insAT		intron	N/A
	PI4KA	ENST00000939414.1		c.6209+220_6209+221insAT		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 32942 AN: 95208 Hom.: 3639 Cov.: 0

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.346 AC: 32979 AN: 95292 Hom.: 3644 Cov.: 0 AF XY: 0.340 AC XY: 15664 AN XY: 46056

African (AFR) AF: 0.301 AC: 6618 AN: 21960

American (AMR) AF: 0.258 AC: 2282 AN: 8828

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 672 AN: 2424

East Asian (EAS) AF: 0.184 AC: 595 AN: 3236

South Asian (SAS) AF: 0.343 AC: 982 AN: 2864

European-Finnish (FIN) AF: 0.386 AC: 2890 AN: 7488

Middle Eastern (MID) AF: 0.304 AC: 56 AN: 184

European-Non Finnish (NFE) AF: 0.393 AC: 18309 AN: 46548

Other (OTH) AF: 0.326 AC: 403 AN: 1238

Alfa AF: 0.237 Hom.: 402

Asia WGS AF: 0.238 AC: 777 AN: 3272

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs373609759; hg19: chr22-21063975;