chrX-129540472-G-A

Position:

• chrX-129540472-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000276.4(OCRL):​c.33G>A​(p.Pro11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000959 in 1,043,265 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 9.6e-7 (0 hom. 0 hem.)
• Consequence: OCRL NM_000276.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant X-129540472-G-A is Benign according to our data. Variant chrX-129540472-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2822912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCRL	NM_000276.4	c.33G>A	p.Pro11=	synonymous_variant	1/24	ENST00000371113.9
OCRL	NM_001318784.2	c.33G>A	p.Pro11=	synonymous_variant	1/24
OCRL	NM_001587.4	c.33G>A	p.Pro11=	synonymous_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCRL	ENST00000371113.9	c.33G>A	p.Pro11=	synonymous_variant	1/24	1	NM_000276.4	P1
OCRL	ENST00000357121.5	c.33G>A	p.Pro11=	synonymous_variant	1/23	1
OCRL	ENST00000691455.1	c.33G>A	p.Pro11=	synonymous_variant, NMD_transcript_variant	1/18
OCRL	ENST00000486673.1	n.91+533G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.59e-7 AC: 1 AN: 1043265 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 340623

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lowe syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1247304752; hg19: chrX-128674449;