rs78516480

Variant names:

• chr22-20709664-T-G
• rs78516480
• NM_058004.4:c.6173+244A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-20709664-T-G
• chr22-20709664-T-A

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.6173+244A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (4833 hom., cov: 14)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.583
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-20709664-T-G is Benign according to our data. Variant chr22-20709664-T-G is described in ClinVar as Benign. ClinVar VariationId is 1178212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 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+244A>C		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6107+244A>C		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.6080+244A>C		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+244A>C		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2546+244A>C		intron	N/A
	PI4KA	ENST00000939414.1		c.6209+244A>C		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 35859 AN: 82834 Hom.: 4835 Cov.: 14

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.433 AC: 35868 AN: 82896 Hom.: 4833 Cov.: 14 AF XY: 0.426 AC XY: 17015 AN XY: 39926

African (AFR) AF: 0.399 AC: 7368 AN: 18474

American (AMR) AF: 0.369 AC: 2692 AN: 7288

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 808 AN: 2140

East Asian (EAS) AF: 0.272 AC: 682 AN: 2508

South Asian (SAS) AF: 0.401 AC: 987 AN: 2460

European-Finnish (FIN) AF: 0.435 AC: 2905 AN: 6680

Middle Eastern (MID) AF: 0.382 AC: 65 AN: 170

European-Non Finnish (NFE) AF: 0.473 AC: 19717 AN: 41654

Other (OTH) AF: 0.415 AC: 447 AN: 1076

Alfa AF: 0.483 Hom.: 1262

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	-0.96
CADD	Benign	3.0
DANN	Benign	0.48
PhyloP100		-0.58
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: rs78516480; hg19: chr22-21063952; COSMIC: COSV55403997; COSMIC: COSV55403997;