chrX-129540456-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_000276.4(OCRL):c.17C>T(p.Pro6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,120,884 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.0000030 ( 0 hom. 1 hem. )

Consequence

OCRL
NM_000276.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.17

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Dent disease type 2
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
oculocerebrorenal syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Laboratory for Molecular Medicine, Orphanet

OCRL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28042632).

BP6

Variant X-129540456-C-T is Benign according to our data. Variant chrX-129540456-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2915085.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000276.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OCRL	NM_000276.4	MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 24	NP_000267.2
OCRL	NM_001318784.2		c.17C>T	p.Pro6Leu	missense	Exon 1 of 24	NP_001305713.1
OCRL	NM_001587.4		c.17C>T	p.Pro6Leu	missense	Exon 1 of 23	NP_001578.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OCRL	ENST00000371113.9	TSL:1 MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 24	ENSP00000360154.4	Q01968-1
OCRL	ENST00000357121.5	TSL:1	c.17C>T	p.Pro6Leu	missense	Exon 1 of 23	ENSP00000349635.5	Q01968-2
OCRL	ENST00000949289.1		c.17C>T	p.Pro6Leu	missense	Exon 1 of 24	ENSP00000619348.1

Frequencies

GnomAD3 genomes

AF:

0.0000191

AC:

AN:

104654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000694

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

GnomAD2 exomes

AF:

0.0000105

AC:

AN:

95693

AF XY:

0.0000285

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000168

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1016230

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

326540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23875

American (AMR)

AF:

0.00

AC:

AN:

26929

Ashkenazi Jewish (ASJ)

AF:

0.0000571

AC:

AN:

17502

East Asian (EAS)

AF:

0.00

AC:

AN:

25019

South Asian (SAS)

AF:

0.00

AC:

AN:

49483

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27297

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2768

European-Non Finnish (NFE)

AF:

0.00000125

AC:

AN:

801098

Other (OTH)

AF:

0.0000237

AC:

AN:

42259

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000191

AC:

AN:

104654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28714

show subpopulations

African (AFR)

AF:

0.0000694

AC:

AN:

28833

American (AMR)

AF:

0.00

AC:

AN:

9994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2572

East Asian (EAS)

AF:

0.00

AC:

AN:

3072

South Asian (SAS)

AF:

0.00

AC:

AN:

1993

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5185

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50740

Other (OTH)

AF:

0.00

AC:

AN:

1402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000121

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lowe syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.4

PhyloP100

3.2

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.41

REVEL

Benign

0.26

Sift

Benign

0.032

Sift4G

Benign

0.18

Polyphen

0.68

Vest4

0.29

MutPred

0.18

Gain of sheet (P = 0.0166)

MVP

0.82

MPC

0.33

ClinPred

0.44

GERP RS

3.9

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.36

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over