10-58225910-C-T

Variant names:

• chr10-58225910-C-T
• rs2790232
• NM_152230.5:c.373+1133G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152230.5(IPMK):​c.373+1133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,024 control chromosomes in the GnomAD database, including 1,326 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 0.083 (1326 hom., cov: 32)
• Consequence: IPMK NM_152230.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• hereditary neuroendocrine tumor of small intestine

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152230.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPMK	NM_152230.5	MANE Select	c.373+1133G>A		intron	N/A	NP_689416.1	Q8NFU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPMK	ENST00000373935.4	TSL:1 MANE Select	c.373+1133G>A		intron	N/A	ENSP00000363046.3	Q8NFU5
	IPMK	ENST00000891909.1		c.382+1133G>A		intron	N/A	ENSP00000561968.1
	IPMK	ENST00000891910.1		c.373+1133G>A		intron	N/A	ENSP00000561969.1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12566 AN: 151908 Hom.: 1320 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0829 AC: 12599 AN: 152024 Hom.: 1326 Cov.: 32 AF XY: 0.0817 AC XY: 6069 AN XY: 74324

African (AFR) AF: 0.247 AC: 10230 AN: 41438

American (AMR) AF: 0.0351 AC: 536 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0515 AC: 248 AN: 4818

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10574

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0188 AC: 1281 AN: 67982

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0426 Hom.: 1570

Bravo AF: 0.0929

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.7
DANN	Benign	0.72
PhyloP100		-0.44
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

Other links and lift over

dbSNP: rs2790232; hg19: chr10-59985671;