Variant 2-190366729-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001128928.2(INPP1):c.300G>T(p.Glu100Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

INPP1
NM_001128928.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

INPP1 (HGNC:6071): (inositol polyphosphate-1-phosphatase) This gene encodes the enzyme inositol polyphosphate-1-phosphatase, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 1 of the inositol ring from the polyphosphates inositol 1,4-bisphosphate and inositol 1,3,4-trisphophosphate. [provided by RefSeq, Jul 2008]

INPP1 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	UniProt
INPP1	NM_001128928.2 linkuse as main transcript	c.300G>T	p.Glu100Asp	missense_variant	5/7	ENST00000392329.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP1	ENST00000392329.7 linkuse as main transcript	c.300G>T	p.Glu100Asp	missense_variant	5/7	5	NM_001128928.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 19, 2022

The c.300G>T (p.E100D) alteration is located in exon 5 (coding exon 3) of the INPP1 gene. This alteration results from a G to T substitution at nucleotide position 300, causing the glutamic acid (E) at amino acid position 100 to be replaced by an aspartic acid (D). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;.;T;.;.;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;.;T;T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.32

T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

M;M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.14

T;T;T;T;T;T;T

Sift4G

Benign

0.38

T;T;T;T;T;T;T

Polyphen

0.68

P;P;.;.;.;.;.

Vest4

0.18

MutPred

0.49

Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);

MVP

0.78

MPC

0.36

ClinPred

0.96

GERP RS

3.7

Varity_R

0.059

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: -1

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