Variant 10-119726345-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014937.4(INPP5F):c.83T>A(p.Leu28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,542 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

INPP5F
NM_014937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.586

Variant links:

Genes affected

INPP5F (HGNC:17054): (inositol polyphosphate-5-phosphatase F) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

INPP5F links:

Genome browser will be placed here

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
INPP5F	NM_014937.4 linkuse as main transcript	c.83T>A	p.Leu28His	missense_variant	1/20	ENST00000650623.2
INPP5F	NM_001243195.2 linkuse as main transcript	c.83T>A	p.Leu28His	missense_variant	1/5
INPP5F	XM_006717720.5 linkuse as main transcript	c.83T>A	p.Leu28His	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5F	ENST00000650623.2 linkuse as main transcript	c.83T>A	p.Leu28His	missense_variant	1/20		NM_014937.4	P1	Q9Y2H2-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

AF:

7.77e-7

AC:

AN:

1287360

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

636764

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151182

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000189

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

Jun 19, 2024

The c.83T>A (p.L28H) alteration is located in exon 1 (coding exon 1) of the INPP5F gene. This alteration results from a T to A substitution at nucleotide position 83, causing the leucine (L) at amino acid position 28 to be replaced by a histidine (H). 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

0.86

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.50

D;.;D;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.75

.;T;T;T;T

M_CAP

Pathogenic

0.76

MetaRNN

Uncertain

0.44

T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.4

L;.;L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.0

N;.;.;.;.

REVEL

Uncertain

0.29

Sift

Uncertain

0.0030

D;.;.;.;.

Sift4G

Uncertain

0.0030

D;.;.;.;.

Polyphen

0.97

D;.;D;D;.

Vest4

0.32

MutPred

0.57

Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);

MVP

0.37

MPC

0.25

ClinPred

0.83

GERP RS

3.7

Varity_R

0.43

gMVP

0.78

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