10-58196368-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152230.5(IPMK):​c.959G>A​(p.Arg320His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

IPMK
NM_152230.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30
Variant links:
Genes affected
IPMK (HGNC:20739): (inositol polyphosphate multikinase) This gene encodes a member of the inositol phosphokinase family. The encoded protein has 3-kinase, 5-kinase and 6-kinase activities on phosphorylated inositol substrates. The encoded protein plays an important role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate, and has a preferred 5-kinase activity. This gene may play a role in nuclear mRNA export. Pseudogenes of this gene are located on the long arm of chromosome 13 and the short arm of chromosome 19. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04232219).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IPMKNM_152230.5 linkc.959G>A p.Arg320His missense_variant Exon 6 of 6 ENST00000373935.4 NP_689416.1 Q8NFU5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IPMKENST00000373935.4 linkc.959G>A p.Arg320His missense_variant Exon 6 of 6 1 NM_152230.5 ENSP00000363046.3 Q8NFU5

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000835
AC:
21
AN:
251386
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000280
AC:
41
AN:
1461816
Hom.:
0
Cov.:
32
AF XY:
0.0000344
AC XY:
25
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000178
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.959G>A (p.R320H) alteration is located in exon 6 (coding exon 6) of the IPMK gene. This alteration results from a G to A substitution at nucleotide position 959, causing the arginine (R) at amino acid position 320 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
19
DANN
Benign
0.35
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.71
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.077
Sift
Benign
0.45
T
Sift4G
Benign
0.21
T
Polyphen
0.0010
B
Vest4
0.098
MVP
0.17
MPC
0.18
ClinPred
0.025
T
GERP RS
3.2
Varity_R
0.026
gMVP
0.19

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: rs535168447; hg19: chr10-59956129; COSMIC: COSV64244886; API