Variant chr22-20709384-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058004.4(PI4KA):c.6174-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 5898 hom., cov: 20)

Exomes 𝑓: 0.087 ( 30130 hom. )

Failed GnomAD Quality Control

Consequence

PI4KA
NM_058004.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001908

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.343

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-20709384-G-A is Benign according to our data. Variant chr22-20709384-G-A is described in ClinVar as [Benign]. Clinvar id is 769146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4 linkuse as main transcript	c.6174-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11 linkuse as main transcript	c.6174-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_058004.4	P1	P42356-1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

30661

AN:

94714

Hom.:

5885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.0869

AC:

15500

AN:

178280

Hom.:

5924

AF XY:

0.0789

AC XY:

7692

AN XY:

97530

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0542

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.0540

Gnomad FIN exome

AF:

0.00515

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0871

AC:

90245

AN:

1036382

Hom.:

30130

Cov.:

AF XY:

0.0904

AC XY:

46643

AN XY:

516052

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.0766

Gnomad4 NFE exome

AF:

0.0668

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.324

AC:

30704

AN:

94804

Hom.:

5898

Cov.:

AF XY:

0.311

AC XY:

14281

AN XY:

45958

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.250

Hom.:

675

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.1

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

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