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GeneBe

10-58227044-G-A

Variant summary

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

The NM_152230.5(IPMK):c.372C>T(p.Asn124=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,593,950 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 10 hom., cov: 33)
Exomes 𝑓: 0.011 ( 149 hom. )

Consequence

IPMK
NM_152230.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.001591
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.921
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 -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=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-58227044-G-A is Benign according to our data. Variant chr10-58227044-G-A is described in ClinVar as [Benign]. Clinvar id is 770963.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=0.921 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0113 (16316/1441750) while in subpopulation MID AF= 0.0312 (165/5290). AF 95% confidence interval is 0.0273. There are 149 homozygotes in gnomad4_exome. There are 8244 alleles in male gnomad4_exome subpopulation. Median coverage is 26. 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 AC in GnomAd at 1419 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IPMKNM_152230.5 linkuse as main transcriptc.372C>T p.Asn124= splice_region_variant, synonymous_variant 3/6 ENST00000373935.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IPMKENST00000373935.4 linkuse as main transcriptc.372C>T p.Asn124= splice_region_variant, synonymous_variant 3/61 NM_152230.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00933
AC:
1419
AN:
152082
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00295
Gnomad AMI
AF:
0.0264
Gnomad AMR
AF:
0.00734
Gnomad ASJ
AF:
0.0346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00600
Gnomad FIN
AF:
0.00208
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0142
Gnomad OTH
AF:
0.0119
GnomAD3 exomes
AF:
0.00957
AC:
2389
AN:
249606
Hom.:
29
AF XY:
0.0100
AC XY:
1351
AN XY:
134938
show subpopulations
Gnomad AFR exome
AF:
0.00210
Gnomad AMR exome
AF:
0.00531
Gnomad ASJ exome
AF:
0.0286
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00681
Gnomad FIN exome
AF:
0.00269
Gnomad NFE exome
AF:
0.0138
Gnomad OTH exome
AF:
0.0102
GnomAD4 exome
AF:
0.0113
AC:
16316
AN:
1441750
Hom.:
149
Cov.:
26
AF XY:
0.0115
AC XY:
8244
AN XY:
718580
show subpopulations
Gnomad4 AFR exome
AF:
0.00331
Gnomad4 AMR exome
AF:
0.00611
Gnomad4 ASJ exome
AF:
0.0319
Gnomad4 EAS exome
AF:
0.0000507
Gnomad4 SAS exome
AF:
0.00663
Gnomad4 FIN exome
AF:
0.00274
Gnomad4 NFE exome
AF:
0.0123
Gnomad4 OTH exome
AF:
0.0119
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00932
AC:
1419
AN:
152200
Hom.:
10
Cov.:
33
AF XY:
0.00898
AC XY:
668
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.00294
Gnomad4 AMR
AF:
0.00733
Gnomad4 ASJ
AF:
0.0346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00601
Gnomad4 FIN
AF:
0.00208
Gnomad4 NFE
AF:
0.0142
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.0141
Hom.:
13
Bravo
AF:
0.00947
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0151
EpiControl
AF:
0.0160

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 testingInvitaeMay 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
12
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0016
dbscSNV1_RF
Benign
0.24
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: rs61749177; hg19: chr10-59986805; COSMIC: COSV99058413; API