Variant chrX-129540456-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_000276.4(OCRL):c.17C>G(p.Pro6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,016,230 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.000014 ( 0 hom. 5 hem. )

Consequence

OCRL
NM_000276.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.17

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:

OCRL (HGNC:):

OCRL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37938103).

BP6

Variant X-129540456-C-G is Benign according to our data. Variant chrX-129540456-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2082205.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCRL	NM_000276.4 linkuse as main transcript	c.17C>G	p.Pro6Arg	missense_variant	1/24	ENST00000371113.9	NP_000267.2	Q01968-1
OCRL	NM_001318784.2 linkuse as main transcript	c.17C>G	p.Pro6Arg	missense_variant	1/24		NP_001305713.1	Q504W7
OCRL	NM_001587.4 linkuse as main transcript	c.17C>G	p.Pro6Arg	missense_variant	1/23		NP_001578.2	Q01968-2A0A2X0TVZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OCRL	ENST00000371113.9 linkuse as main transcript	c.17C>G	p.Pro6Arg	missense_variant	1/24	1	NM_000276.4	ENSP00000360154.4	Q01968-1
OCRL	ENST00000357121.5 linkuse as main transcript	c.17C>G	p.Pro6Arg	missense_variant	1/23	1		ENSP00000349635.5	Q01968-2
OCRL	ENST00000691455.1 linkuse as main transcript	n.17C>G		non_coding_transcript_exon_variant	1/18			ENSP00000510265.1	A0A8I5KYX7
OCRL	ENST00000486673.1 linkuse as main transcript	n.91+517C>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000105

AC:

AN:

95693

Hom.:

AF XY:

0.00

AC XY:

AN XY:

35065

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000130

Gnomad SAS 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:

0.0000138

AC:

AN:

1016230

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

326540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000202

Gnomad4 FIN exome

AF:

0.0000366

Gnomad4 NFE exome

AF:

0.0000125

Gnomad4 OTH exome

AF:

0.0000237

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lowe syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.74

T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.37

N;N

REVEL

Uncertain

0.29

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.21

T;T

Polyphen

0.48

P;D

Vest4

0.39

MutPred

0.18

Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);

MVP

0.80

MPC

0.49

ClinPred

0.28

GERP RS

3.9

Varity_R

0.12

gMVP

0.37

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