22-20710068-A-C

Variant names:

• chr22-20710068-A-C
• rs5760149
• NM_058004.4:c.6084-71T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058004.4(PI4KA):​c.6084-71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 834,838 control chromosomes in the GnomAD database, including 82,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (16958 hom., cov: 33)
  • Exomes 𝑓: 0.43 (65604 hom.)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.11
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-20710068-A-C is Benign according to our data. Variant chr22-20710068-A-C is described in ClinVar as Benign. ClinVar VariationId is 1275198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 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.6084-71T>G		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6018-71T>G		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.5991-71T>G		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.6084-71T>G		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2457-71T>G		intron	N/A
	PI4KA	ENST00000939414.1		c.6120-71T>G		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71113 AN: 151578 Hom.: 16938 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.434 AC: 296647 AN: 683140 Hom.: 65604 Cov.: 9 AF XY: 0.432 AC XY: 158421 AN XY: 366978

African (AFR) AF: 0.528 AC: 9710 AN: 18406

American (AMR) AF: 0.571 AC: 23583 AN: 41324

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 10093 AN: 20980

East Asian (EAS) AF: 0.522 AC: 18452 AN: 35368

South Asian (SAS) AF: 0.387 AC: 26977 AN: 69752

European-Finnish (FIN) AF: 0.294 AC: 15029 AN: 51058

Middle Eastern (MID) AF: 0.469 AC: 1920 AN: 4098

European-Non Finnish (NFE) AF: 0.430 AC: 175429 AN: 407562

Other (OTH) AF: 0.447 AC: 15454 AN: 34592

GnomAD4 genome AF: 0.469 AC: 71179 AN: 151698 Hom.: 16958 Cov.: 33 AF XY: 0.463 AC XY: 34322 AN XY: 74144

African (AFR) AF: 0.527 AC: 21804 AN: 41352

American (AMR) AF: 0.529 AC: 8058 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1663 AN: 3460

East Asian (EAS) AF: 0.527 AC: 2697 AN: 5120

South Asian (SAS) AF: 0.400 AC: 1923 AN: 4804

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10562

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30282 AN: 67852

Other (OTH) AF: 0.500 AC: 1050 AN: 2102

Alfa AF: 0.461 Hom.: 1974

Bravo AF: 0.494

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.55
DANN	Benign	0.53
PhyloP100		-1.1
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: rs5760149; hg19: chr22-21064356; COSMIC: COSV55420559; COSMIC: COSV55420559;