rs1856564

Variant names:

• chr10-58257691-G-A
• rs1856564
• NM_152230.5:c.190+9731C>T

Variant summary

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

The NM_152230.5(IPMK):​c.190+9731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,820 control chromosomes in the GnomAD database, including 10,940 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 0.34 (10940 hom., cov: 32)
• Consequence: IPMK NM_152230.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 8 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPMK	NM_152230.5	c.190+9731C>T		intron_variant	Intron 1 of 5	ENST00000373935.4	NP_689416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPMK	ENST00000373935.4	c.190+9731C>T		intron_variant	Intron 1 of 5	1	NM_152230.5	ENSP00000363046.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51318 AN: 151702 Hom.: 10906 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.339 AC: 51406 AN: 151820 Hom.: 10940 Cov.: 32 AF XY: 0.338 AC XY: 25086 AN XY: 74208

African (AFR) AF: 0.607 AC: 25133 AN: 41382

American (AMR) AF: 0.236 AC: 3601 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 786 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2301 AN: 5156

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4814

European-Finnish (FIN) AF: 0.220 AC: 2311 AN: 10486

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15090 AN: 67948

Other (OTH) AF: 0.284 AC: 601 AN: 2116

Alfa AF: 0.315 Hom.: 1172

Bravo AF: 0.353

Asia WGS AF: 0.322 AC: 1120 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		0.061
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: rs1856564; hg19: chr10-60017452;