10-58193285-G-C

Variant names:

• chr10-58193285-G-C
• rs17636964
• NM_152230.5:c.*2791C>G

Variant summary

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

The NM_152230.5(IPMK):​c.*2791C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,712 control chromosomes in the GnomAD database, including 1,750 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 0.13 (1750 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IPMK NM_152230.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPMK	NM_152230.5	c.*2791C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000373935.4	NP_689416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPMK	ENST00000373935.4	c.*2791C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_152230.5	ENSP00000363046.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20275 AN: 151594 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.165

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.134 AC: 20273 AN: 151712 Hom.: 1750 Cov.: 32 AF XY: 0.130 AC XY: 9613 AN XY: 74142

African (AFR) AF: 0.0337 AC: 1400 AN: 41496

American (AMR) AF: 0.129 AC: 1973 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3462

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5178

South Asian (SAS) AF: 0.100 AC: 484 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1863 AN: 10530

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13352 AN: 67668

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.0725 Hom.: 88

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.43
PhyloP100		-1.6
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: rs17636964; hg19: chr10-59953046;