10-58196644-G-A

Position:

• chr10-58196644-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152230.5(IPMK):​c.683C>T​(p.Ala228Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IPMK NM_152230.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3726403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPMK	NM_152230.5	c.683C>T	p.Ala228Val	missense_variant	6/6	ENST00000373935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPMK	ENST00000373935.4	c.683C>T	p.Ala228Val	missense_variant	6/6	1	NM_152230.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.683C>T (p.A228V) alteration is located in exon 6 (coding exon 6) of the IPMK gene. This alteration results from a C to T substitution at nucleotide position 683, causing the alanine (A) at amino acid position 228 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.015	D
Sift4G	Benign	0.096	T
Polyphen		0.95	P
Vest4		0.27
MutPred		0.49		Gain of catalytic residue at A228 (P = 0.1766);
MVP		0.34
MPC		0.42
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-59956405;