rs1132816

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005028.5(PIP4K2A):​c.30T>C​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,608,664 control chromosomes in the GnomAD database, including 62,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 9306 hom., cov: 30)
Exomes 𝑓: 0.26 ( 53059 hom. )

Consequence

PIP4K2A
NM_005028.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

17 publications found
Variant links:
Genes affected
PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP7
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIP4K2ANM_005028.5 linkc.30T>C p.Ser10Ser synonymous_variant Exon 1 of 10 ENST00000376573.9 NP_005019.2 P48426-1
PIP4K2AXM_006717450.3 linkc.30T>C p.Ser10Ser synonymous_variant Exon 1 of 9 XP_006717513.1
PIP4K2ANM_001330062.2 linkc.-395T>C upstream_gene_variant NP_001316991.1 P48426-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIP4K2AENST00000376573.9 linkc.30T>C p.Ser10Ser synonymous_variant Exon 1 of 10 1 NM_005028.5 ENSP00000365757.4 P48426-1
PIP4K2AENST00000545335.5 linkc.-395T>C upstream_gene_variant 2 ENSP00000442098.1 P48426-2

Frequencies

GnomAD3 genomes
AF:
0.321
AC:
48556
AN:
151294
Hom.:
9283
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.543
Gnomad AMI
AF:
0.206
Gnomad AMR
AF:
0.207
Gnomad ASJ
AF:
0.187
Gnomad EAS
AF:
0.103
Gnomad SAS
AF:
0.275
Gnomad FIN
AF:
0.171
Gnomad MID
AF:
0.306
Gnomad NFE
AF:
0.264
Gnomad OTH
AF:
0.293
GnomAD2 exomes
AF:
0.247
AC:
60081
AN:
243608
AF XY:
0.247
show subpopulations
Gnomad AFR exome
AF:
0.559
Gnomad AMR exome
AF:
0.134
Gnomad ASJ exome
AF:
0.196
Gnomad EAS exome
AF:
0.116
Gnomad FIN exome
AF:
0.187
Gnomad NFE exome
AF:
0.262
Gnomad OTH exome
AF:
0.243
GnomAD4 exome
AF:
0.262
AC:
381471
AN:
1457252
Hom.:
53059
Cov.:
33
AF XY:
0.261
AC XY:
189544
AN XY:
725108
show subpopulations
African (AFR)
AF:
0.556
AC:
18401
AN:
33092
American (AMR)
AF:
0.143
AC:
6348
AN:
44460
Ashkenazi Jewish (ASJ)
AF:
0.195
AC:
5055
AN:
25948
East Asian (EAS)
AF:
0.0767
AC:
3003
AN:
39142
South Asian (SAS)
AF:
0.283
AC:
24386
AN:
86044
European-Finnish (FIN)
AF:
0.190
AC:
10109
AN:
53114
Middle Eastern (MID)
AF:
0.290
AC:
1669
AN:
5758
European-Non Finnish (NFE)
AF:
0.267
AC:
296432
AN:
1109572
Other (OTH)
AF:
0.267
AC:
16068
AN:
60122
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
13583
27166
40748
54331
67914
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10028
20056
30084
40112
50140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.321
AC:
48628
AN:
151412
Hom.:
9306
Cov.:
30
AF XY:
0.312
AC XY:
23095
AN XY:
74014
show subpopulations
African (AFR)
AF:
0.543
AC:
22436
AN:
41288
American (AMR)
AF:
0.206
AC:
3150
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.187
AC:
646
AN:
3462
East Asian (EAS)
AF:
0.102
AC:
523
AN:
5112
South Asian (SAS)
AF:
0.275
AC:
1318
AN:
4798
European-Finnish (FIN)
AF:
0.171
AC:
1790
AN:
10462
Middle Eastern (MID)
AF:
0.315
AC:
92
AN:
292
European-Non Finnish (NFE)
AF:
0.264
AC:
17869
AN:
67730
Other (OTH)
AF:
0.294
AC:
618
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1514
3028
4542
6056
7570
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
454
908
1362
1816
2270
<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:
0.290
Hom.:
3692
Bravo
AF:
0.333
Asia WGS
AF:
0.221
AC:
770
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.1
DANN
Benign
0.61
PhyloP100
-1.5
PromoterAI
0.052
Neutral
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1132816; hg19: chr10-23003226; COSMIC: COSV64862525; COSMIC: COSV64862525; API