22-20710746-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_058004.4(PI4KA):​c.6036C>T​(p.Pro2012Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 151,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PI4KA
NM_058004.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.0770
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 22-20710746-G-A is Benign according to our data. Variant chr22-20710746-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 784557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20710746-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000686 (104/151600) while in subpopulation NFE AF= 0.00107 (72/67430). AF 95% confidence interval is 0.000869. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PI4KANM_058004.4 linkc.6036C>T p.Pro2012Pro synonymous_variant Exon 52 of 55 ENST00000255882.11 NP_477352.3 P42356-1Q4LE69B4DYG5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PI4KAENST00000255882.11 linkc.6036C>T p.Pro2012Pro synonymous_variant Exon 52 of 55 1 NM_058004.4 ENSP00000255882.6 P42356-1

Frequencies

GnomAD3 genomes
AF:
0.000687
AC:
104
AN:
151482
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00443
Gnomad AMR
AF:
0.000590
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00107
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00222
AC:
556
AN:
250464
Hom.:
0
AF XY:
0.00243
AC XY:
329
AN XY:
135420
show subpopulations
Gnomad AFR exome
AF:
0.000801
Gnomad AMR exome
AF:
0.000811
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00186
Gnomad FIN exome
AF:
0.00166
Gnomad NFE exome
AF:
0.00343
Gnomad OTH exome
AF:
0.00343
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00227
AC:
3307
AN:
1454324
Hom.:
0
Cov.:
32
AF XY:
0.00222
AC XY:
1608
AN XY:
723440
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.000628
Gnomad4 ASJ exome
AF:
0.000767
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000919
Gnomad4 FIN exome
AF:
0.000732
Gnomad4 NFE exome
AF:
0.00273
Gnomad4 OTH exome
AF:
0.00171
GnomAD4 genome
AF:
0.000686
AC:
104
AN:
151600
Hom.:
0
Cov.:
33
AF XY:
0.000715
AC XY:
53
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00107
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00420
Hom.:
0

ClinVar

Significance: Benign/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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023PI4KA: BP4, BP7 -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 19, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
9.5
DANN
Benign
0.61
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs150339960; hg19: chr22-21065034; COSMIC: COSV55425005; COSMIC: COSV55425005; API