22-20709687-A-AAT

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.6173+220_6173+221insAT		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.6173+220_6173+221insAT		intron_variant		1	NM_058004.4	P1

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

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.326

Alfa AF: 0.237 Hom.: 402

Asia WGS AF: 0.238 AC: 777 AN: 3272

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373609759; hg19: chr22-21063975;