Variant 10-58227044-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_152230.5(IPMK):c.372C>T(p.Asn124Asn) 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

Splicing: ADA: 0.001591

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

IPMK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.921 with no splicing effect.

BS1

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

High AC in GnomAd4 at 1419 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPMK	NM_152230.5 linkuse as main transcript	c.372C>T	p.Asn124Asn	splice_region_variant, synonymous_variant	3/6	ENST00000373935.4	NP_689416.1	Q8NFU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPMK	ENST00000373935.4 linkuse as main transcript	c.372C>T	p.Asn124Asn	splice_region_variant, synonymous_variant	3/6	1	NM_152230.5	ENSP00000363046.3		Q8NFU5

Frequencies

GnomAD3 genomes

AF:

0.00933

AC:

1419

AN:

152082

Hom.:

Cov.:

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.:

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.:

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

AF:

0.00932

AC:

1419

AN:

152200

Hom.:

Cov.:

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.:

Bravo

AF:

0.00947

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0151

EpiControl

AF:

0.0160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over