rs747396791

chrX-129558664-T-AchrX-129558664-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_000276.4(OCRL):c.471T>A(p.Ser157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,210,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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). Synonymous variant affecting the same amino acid position (i.e. S157S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: OCRL NM_000276.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.946

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-129558664-T-A is Benign according to our data. Variant chrX-129558664-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287429.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.946 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCRL	NM_000276.4	c.471T>A	p.Ser157=	synonymous_variant	7/24	ENST00000371113.9
OCRL	NM_001318784.2	c.474T>A	p.Ser158=	synonymous_variant	7/24
OCRL	NM_001587.4	c.471T>A	p.Ser157=	synonymous_variant	7/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCRL	ENST00000371113.9	c.471T>A	p.Ser157=	synonymous_variant	7/24	1	NM_000276.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 3 AN: 112807 Hom.: 0 Cov.: 23 AF XY: 0.0000859 AC XY: 3 AN XY: 34941

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000281

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: 0.0000164 AC: 3 AN: 182956 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67674

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

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: 0.00000547 AC: 6 AN: 1097732 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000852

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: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000266 AC: 3 AN: 112860 Hom.: 0 Cov.: 23 AF XY: 0.0000857 AC XY: 3 AN XY: 35004

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000280

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

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 04, 2016

- -

Lowe syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.2
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs747396791; hg19: chrX-128692641;