Variant 10-119805392-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014937.4(INPP5F):c.1250T>C(p.Met417Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000295 in 1,611,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

INPP5F
NM_014937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16881686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP5F	NM_014937.4 linkuse as main transcript	c.1250T>C	p.Met417Thr	missense_variant	11/20	ENST00000650623.2
LOC105378513	XR_946359.3 linkuse as main transcript	n.465-695A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5F	ENST00000650623.2 linkuse as main transcript	c.1250T>C	p.Met417Thr	missense_variant	11/20		NM_014937.4	P1	Q9Y2H2-1
	ENST00000636592.1 linkuse as main transcript	n.744+9096A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000303

AC:

AN:

250972

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000116

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:

0.000590

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000293

AC:

428

AN:

1459648

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

226

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000360

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000309

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000510

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000492

EpiControl

AF:

0.000593

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

Oct 18, 2021

The c.1250T>C (p.M417T) alteration is located in exon 11 (coding exon 11) of the INPP5F gene. This alteration results from a T to C substitution at nucleotide position 1250, causing the methionine (M) at amino acid position 417 to be replaced by a threonine (T). 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

1.0

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.0

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.61

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

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.032

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.3

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

REVEL

Benign

0.28

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.0020

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

Polyphen

0.32

B;.;B;.;.;.;.

Vest4

0.75

MVP

0.40

MPC

0.29

ClinPred

0.57

GERP RS

4.5

Varity_R

0.73

gMVP

0.75

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