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GeneBe

10-22537249-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005028.5(PIP4K2A):c.1173A>G(p.Glu391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,606,956 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 49 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 68 hom. )

Consequence

PIP4K2A
NM_005028.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86
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]

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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=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-22537249-T-C is Benign according to our data. Variant chr10-22537249-T-C is described in ClinVar as [Benign]. Clinvar id is 779110.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=1.86 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIP4K2ANM_005028.5 linkuse as main transcriptc.1173A>G p.Glu391= synonymous_variant 10/10 ENST00000376573.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIP4K2AENST00000376573.9 linkuse as main transcriptc.1173A>G p.Glu391= synonymous_variant 10/101 NM_005028.5 P1P48426-1
PIP4K2AENST00000545335.5 linkuse as main transcriptc.996A>G p.Glu332= synonymous_variant 10/102 P48426-2
PIP4K2AENST00000323883.11 linkuse as main transcriptc.753A>G p.Glu251= synonymous_variant 8/82
PIP4K2AENST00000474335.1 linkuse as main transcriptn.203A>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0155
AC:
2362
AN:
152134
Hom.:
49
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0526
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00811
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000367
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00420
AC:
1008
AN:
239906
Hom.:
22
AF XY:
0.00297
AC XY:
384
AN XY:
129420
show subpopulations
Gnomad AFR exome
AF:
0.0534
Gnomad AMR exome
AF:
0.00386
Gnomad ASJ exome
AF:
0.00144
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000241
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000316
Gnomad OTH exome
AF:
0.00388
GnomAD4 exome
AF:
0.00182
AC:
2647
AN:
1454704
Hom.:
68
Cov.:
31
AF XY:
0.00160
AC XY:
1153
AN XY:
722866
show subpopulations
Gnomad4 AFR exome
AF:
0.0547
Gnomad4 AMR exome
AF:
0.00513
Gnomad4 ASJ exome
AF:
0.00170
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000188
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.00446
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0156
AC:
2370
AN:
152252
Hom.:
49
Cov.:
32
AF XY:
0.0148
AC XY:
1104
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0527
Gnomad4 AMR
AF:
0.00810
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000368
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00707
Hom.:
14
Bravo
AF:
0.0174
Asia WGS
AF:
0.00491
AC:
17
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 09, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
7.1
Dann
Benign
0.50

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.

Other links and lift over

dbSNP: rs80142698; hg19: chr10-22826178; API