Genetic Variant IP6K1:p.Pro378Ser (chr3-49727316-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153273.4(IP6K1):c.1132C>T(p.Pro378Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IP6K1
NM_153273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07124588).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IP6K1	NM_153273.4	MANE Select	c.1132C>T	p.Pro378Ser	missense	Exon 6 of 6	NP_695005.1	Q92551-1
IP6K1	NM_001242829.2		c.1132C>T	p.Pro378Ser	missense	Exon 6 of 6	NP_001229758.1	Q92551-1
IP6K1	NM_001006115.3		c.637C>T	p.Pro213Ser	missense	Exon 5 of 5	NP_001006115.1	Q92551-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IP6K1	ENST00000321599.9	TSL:1 MANE Select	c.1132C>T	p.Pro378Ser	missense	Exon 6 of 6	ENSP00000323780.4	Q92551-1
IP6K1	ENST00000613416.4	TSL:5	c.1132C>T	p.Pro378Ser	missense	Exon 6 of 6	ENSP00000482032.1	Q92551-1
IP6K1	ENST00000853567.1		c.1132C>T	p.Pro378Ser	missense	Exon 7 of 7	ENSP00000523626.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727224

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60392

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

M_CAP

Benign

0.0042

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

3.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.59

REVEL

Benign

0.034

Sift

Benign

0.71

Sift4G

Benign

0.89

Polyphen

0.0060

Vest4

0.10

MutPred

0.32

Loss of glycosylation at P378 (P = 0.0211)

MVP

0.29

MPC

0.82

ClinPred

0.44

GERP RS

4.7

Varity_R

0.037

gMVP

0.25

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over