Variant 3-49727514-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153273.4(IP6K1):c.934C>G(p.Leu312Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

IP6K1
NM_153273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

Variant links:

Genes affected

IP6K1 (HGNC:18360): (inositol hexakisphosphate kinase 1) This gene encodes a member of the inositol phosphokinase family. The encoded protein may be 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. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

IP6K1 links:

IP6K1 (HGNC:):

IP6K1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IP6K1	NM_153273.4 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	6/6	ENST00000321599.9	NP_695005.1	Q92551-1A0A024R2X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IP6K1	ENST00000321599.9 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	6/6	1	NM_153273.4	ENSP00000323780.4		Q92551-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251036

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000274

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

Bravo

AF:

0.00000756

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

Oct 12, 2022

The c.934C>G (p.L312V) alteration is located in exon 6 (coding exon 5) of the IP6K1 gene. This alteration results from a C to G substitution at nucleotide position 934, causing the leucine (L) at amino acid position 312 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

0.10

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

.;D;D;.

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.5

N;.;N;N

REVEL

Benign

0.19

Sift

Benign

0.050

D;.;T;T

Sift4G

Benign

0.073

T;T;T;T

Polyphen

0.97

D;D;.;.

Vest4

0.58

MutPred

0.66

Gain of glycosylation at S313 (P = 0.0674);Gain of glycosylation at S313 (P = 0.0674);.;.;

MVP

0.39

MPC

1.9

ClinPred

0.59

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.65

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