Variant rs749551841 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000276.4(OCRL):c.2695G>A(p.Glu899Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,097,965 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000014 ( 0 hom. 6 hem. )

Failed GnomAD Quality Control

Consequence

OCRL
NM_000276.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.42

Variant links:

Genes affected

OCRL (HGNC:8108): (OCRL inositol polyphosphate-5-phosphatase) This gene encodes an inositol polyphosphate 5-phosphatase. This protein is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane. This protein may also play a role in primary cilium formation. Mutations in this gene cause oculocerebrorenal syndrome of Lowe and also Dent disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OCRL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25941175).

BP6

Variant X-129590259-G-A is Benign according to our data. Variant chrX-129590259-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 377044.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OCRL	NM_000276.4 linkuse as main transcript	c.2695G>A	p.Glu899Lys	missense_variant	24/24	ENST00000371113.9
OCRL	NM_001318784.2 linkuse as main transcript	c.2698G>A	p.Glu900Lys	missense_variant	24/24
OCRL	NM_001587.4 linkuse as main transcript	c.2671G>A	p.Glu891Lys	missense_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCRL	ENST00000371113.9 linkuse as main transcript	c.2695G>A	p.Glu899Lys	missense_variant	24/24	1	NM_000276.4	P1	Q01968-1

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

111024

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33236

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

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

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183300

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67790

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:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1097965

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363343

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000901

AC:

AN:

111024

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33236

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Dec 29, 2016

- -

Lowe syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.53

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.086

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.15

B;P

Vest4

0.049

MutPred

0.47

Gain of ubiquitination at E899 (P = 0.023);.;

MVP

0.82

MPC

0.68

ClinPred

0.27

GERP RS

5.5

Varity_R

0.20

gMVP

0.27

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