chrX-129540488-G-A

Position:

chrX-129540488-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000276.4(OCRL):c.39+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,147,905 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 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 0.0011 ( 0 hom., 15 hem., cov: 20)

Exomes 𝑓: 0.00011 ( 0 hom. 28 hem. )

Consequence

OCRL
NM_000276.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -1.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-129540488-G-A is Benign according to our data. Variant chrX-129540488-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193072.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00109 (117/106894) while in subpopulation AFR AF= 0.00379 (111/29318). AF 95% confidence interval is 0.00321. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
OCRL	NM_000276.4 linkuse as main transcript	c.39+10G>A	intron_variant	ENST00000371113.9	NP_000267.2	Q01968-1
OCRL	NM_001318784.2 linkuse as main transcript	c.39+10G>A	intron_variant		NP_001305713.1	Q504W7
OCRL	NM_001587.4 linkuse as main transcript	c.39+10G>A	intron_variant		NP_001578.2	Q01968-2A0A2X0TVZ9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
OCRL	ENST00000371113.9 linkuse as main transcript	c.39+10G>A	intron_variant	1	NM_000276.4	ENSP00000360154.4	Q01968-1
OCRL	ENST00000357121.5 linkuse as main transcript	c.39+10G>A	intron_variant	1		ENSP00000349635.5	Q01968-2
OCRL	ENST00000486673.1 linkuse as main transcript	n.91+549G>A	intron_variant	5
OCRL	ENST00000691455.1 linkuse as main transcript	n.39+10G>A	intron_variant			ENSP00000510265.1	A0A8I5KYX7

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

117

AN:

106853

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

29379

show subpopulations

Gnomad AFR

AF:

0.00379

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000195

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:

0.0000392

Gnomad OTH

AF:

0.00141

GnomAD3 exomes

AF:

0.000337

AC:

AN:

95065

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

34717

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.000209

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

116

AN:

1041011

Hom.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

338469

show subpopulations

Gnomad4 AFR exome

AF:

0.00405

Gnomad4 AMR exome

AF:

0.000216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000245

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00109

AC:

117

AN:

106894

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

29430

show subpopulations

Gnomad4 AFR

AF:

0.00379

Gnomad4 AMR

AF:

0.000194

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000392

Gnomad4 OTH

AF:

0.00139

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.00143

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 11, 2015

- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 20, 2022

- -

Lowe syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

OCRL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.5

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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