Variant chr6-33723034-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_054111.5(IP6K3):c.919C>G(p.Arg307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IP6K3
NM_054111.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Variant links:

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]

IP6K3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12535799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IP6K3	NM_054111.5 linkuse as main transcript	c.919C>G	p.Arg307Gly	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 linkuse as main transcript	c.919C>G	p.Arg307Gly	missense_variant	6/6	1	NM_054111.5	ENSP00000293756	P1
IP6K3	ENST00000451316.6 linkuse as main transcript	c.919C>G	p.Arg307Gly	missense_variant	7/7	2		ENSP00000398861	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251278

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2023

The c.919C>G (p.R307G) alteration is located in exon 7 (coding exon 5) of the IP6K3 gene. This alteration results from a C to G substitution at nucleotide position 919, causing the arginine (R) at amino acid position 307 to be replaced by a glycine (G). 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

0.092

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.024

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

0.21

B;B

Vest4

0.094

MutPred

0.52

Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);

MVP

0.35

MPC

0.40

ClinPred

0.23

GERP RS

4.1

Varity_R

0.23

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over