6-33723082-C-T

Position:

• chr6-33723082-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_054111.5(IP6K3):​c.871G>A​(p.Gly291Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IP6K3 NM_054111.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

IP6K3 (HGNC:17269): (inositol hexakisphosphate kinase 3) This gene encodes a protein that belongs to the inositol phosphokinase (IPK) family. This protein is likely responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IP6K3	NM_054111.5	c.871G>A	p.Gly291Arg	missense_variant	6/6	ENST00000293756.5	NP_473452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IP6K3	ENST00000293756.5	c.871G>A	p.Gly291Arg	missense_variant	6/6	1	NM_054111.5	ENSP00000293756	P1
IP6K3	ENST00000451316.6	c.871G>A	p.Gly291Arg	missense_variant	7/7	2		ENSP00000398861	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 08, 2024

The c.871G>A (p.G291R) alteration is located in exon 7 (coding exon 5) of the IP6K3 gene. This alteration results from a G to A substitution at nucleotide position 871, causing the glycine (G) at amino acid position 291 to be replaced by an arginine (R). 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.072	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-7.1	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.67		Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);
MVP		0.67
MPC		0.82
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.81
gMVP		0.66

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: chr6-33690859;