Variant 4-142122201-C-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_001101669.3(INPP4B):c.2062G>A(p.Asp688Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

INPP4B
NM_001101669.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.26

Variant links:

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

INPP4B 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
INPP4B	NM_001101669.3 linkuse as main transcript	c.2062G>A	p.Asp688Asn	missense_variant	21/26	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9 linkuse as main transcript	c.2062G>A	p.Asp688Asn	missense_variant	21/26	5	NM_001101669.3	ENSP00000262992	P3	O15327-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459598

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726076

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:

0.0000375

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000614

Hom.:

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

Sep 13, 2023

The c.2062G>A (p.D688N) alteration is located in exon 22 (coding exon 18) of the INPP4B gene. This alteration results from a G to A substitution at nucleotide position 2062, causing the aspartic acid (D) at amino acid position 688 to be replaced by an asparagine (N). 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

0.60

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

D;D;D;T;T;.;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.74

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

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.5

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

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0080

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

Polyphen

1.0

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

Vest4

0.88

MutPred

0.62

Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);.;Gain of MoRF binding (P = 0.0526);.;

MVP

0.64

MPC

0.74

ClinPred

1.0

GERP RS

5.9

Varity_R

0.70

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over