X-129540456-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 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

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 2915085.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OCRL	NM_000276.4 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant	1/24	ENST00000371113.9
OCRL	NM_001318784.2 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant	1/24
OCRL	NM_001587.4 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCRL	ENST00000371113.9 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant	1/24	1	NM_000276.4	P1	Q01968-1
OCRL	ENST00000357121.5 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant	1/23	1			Q01968-2
OCRL	ENST00000691455.1 linkuse as main transcript	c.17C>T	p.Pro6Leu	missense_variant, NMD_transcript_variant	1/18
OCRL	ENST00000486673.1 linkuse as main transcript	n.91+517C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000191

AC:

AN:

104654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28714

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

GnomAD3 exomes

AF:

0.0000105

AC:

AN:

95693

Hom.:

AF XY:

0.0000285

AC XY:

AN XY:

35065

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 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:

0.00000295

AC:

AN:

1016230

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

326540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000571

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000125

Gnomad4 OTH exome

AF:

0.0000237

GnomAD4 genome

AF:

0.0000191

AC:

AN:

104654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28714

show subpopulations

Gnomad4 AFR

AF:

0.0000694

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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000121

AC:

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

Invitae

Jul 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.83

T;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.28

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.26

Sift

Benign

0.032

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.68

P;P

Vest4

0.29

MutPred

0.18

Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);

MVP

0.82

MPC

0.33

ClinPred

0.44

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.36

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