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GeneBe

22-20710827-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_058004.4(PI4KA):c.5955C>T(p.Gly1985=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,612,056 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

PI4KA
NM_058004.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.46
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-20710827-G-A is Benign according to our data. Variant chr22-20710827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790232.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.46 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (882/152074) while in subpopulation AFR AF= 0.0197 (816/41488). AF 95% confidence interval is 0.0185. There are 2 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PI4KANM_058004.4 linkuse as main transcriptc.5955C>T p.Gly1985= synonymous_variant 52/55 ENST00000255882.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PI4KAENST00000255882.11 linkuse as main transcriptc.5955C>T p.Gly1985= synonymous_variant 52/551 NM_058004.4 P1P42356-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00579
AC:
880
AN:
151960
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0197
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00314
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00134
AC:
335
AN:
250320
Hom.:
0
AF XY:
0.000967
AC XY:
131
AN XY:
135514
show subpopulations
Gnomad AFR exome
AF:
0.0183
Gnomad AMR exome
AF:
0.000897
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.000591
AC:
863
AN:
1459982
Hom.:
2
Cov.:
31
AF XY:
0.000496
AC XY:
360
AN XY:
726398
show subpopulations
Gnomad4 AFR exome
AF:
0.0200
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00580
AC:
882
AN:
152074
Hom.:
2
Cov.:
33
AF XY:
0.00557
AC XY:
414
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0197
Gnomad4 AMR
AF:
0.00314
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.000305
Hom.:
0
Bravo
AF:
0.00675

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeSep 21, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
0.13
Dann
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs144997356; hg19: chr22-21065115; API