Variant chr22-20707880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_058004.4(PI4KA):c.*167G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 744,930 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 100 hom., cov: 30)

Exomes 𝑓: 0.040 ( 595 hom. )

Consequence

PI4KA
NM_058004.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.411

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-20707880-C-T is Benign according to our data. Variant chr22-20707880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1320583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0333 (5072/152328) while in subpopulation NFE AF= 0.05 (3403/68028). AF 95% confidence interval is 0.0486. There are 100 homozygotes in gnomad4. There are 2475 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4 linkuse as main transcript	c.*167G>A		3_prime_UTR_variant	55/55	ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11 linkuse as main transcript	c.*167G>A		3_prime_UTR_variant	55/55	1	NM_058004.4	P1	P42356-1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5074

AN:

152210

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00914

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0403

AC:

23894

AN:

592602

Hom.:

595

Cov.:

AF XY:

0.0403

AC XY:

12975

AN XY:

321756

show subpopulations

Gnomad4 AFR exome

AF:

0.00898

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.000197

Gnomad4 SAS exome

AF:

0.0314

Gnomad4 FIN exome

AF:

0.0415

Gnomad4 NFE exome

AF:

0.0497

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0333

AC:

5072

AN:

152328

Hom.:

100

Cov.:

AF XY:

0.0332

AC XY:

2475

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00912

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.0414

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0447

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.7

DANN

Benign

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over