Genetic Variant PI4KA:c.6173+220_6173+221insAT (chr22-20709687-A-AAT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.291

Publications

1 publications found

Variant links:

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)

PI4KA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

AF XY:

0.340

AC XY:

15664

AN XY:

46056

show subpopulations

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:

AN:

184

European-Non Finnish (NFE)

AF:

0.393

AC:

18309

AN:

46548

Other (OTH)

AF:

0.326

AC:

403

AN:

1238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

742

1484

2225

2967

3709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over