Variant 2-190362629-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001128928.2(INPP1):c.207T>G(p.Phe69Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000186 in 1,454,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

INPP1
NM_001128928.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP1	NM_001128928.2 link	c.207T>G	p.Phe69Leu	missense_variant, splice_region_variant	4/7	ENST00000392329.7	NP_001122400.1	P49441Q6IBG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP1	ENST00000392329.7 link	c.207T>G	p.Phe69Leu	missense_variant, splice_region_variant	4/7	5	NM_001128928.2	ENSP00000376142.2		P49441

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248630

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1454002

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

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 27, 2024

The c.207T>G (p.F69L) alteration is located in exon 4 (coding exon 2) of the INPP1 gene. This alteration results from a T to G substitution at nucleotide position 207, causing the phenylalanine (F) at amino acid position 69 to be replaced by a leucine (L). 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

0.96

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

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

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.87

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.3

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

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.2

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Benign

0.062

T;T;T;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;.;.;.

Vest4

0.65

MutPred

0.82

Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);Loss of methylation at K68 (P = 0.0295);

MVP

0.69

MPC

0.96

ClinPred

0.99

GERP RS

5.8

Varity_R

0.85

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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