chrX-129540460-C-T

Position:

• chrX-129540460-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000276.4(OCRL):​c.21C>T​(p.Val7Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000974 in 1,027,044 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 (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.7e-7 (0 hom. 1 hem.)
• Consequence: OCRL NM_000276.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0700

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-129540460-C-T is Benign according to our data. Variant chrX-129540460-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2817327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.07 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCRL	NM_000276.4	c.21C>T	p.Val7Val	synonymous_variant	1/24	ENST00000371113.9	NP_000267.2
OCRL	NM_001318784.2	c.21C>T	p.Val7Val	synonymous_variant	1/24		NP_001305713.1
OCRL	NM_001587.4	c.21C>T	p.Val7Val	synonymous_variant	1/23		NP_001578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCRL	ENST00000371113.9	c.21C>T	p.Val7Val	synonymous_variant	1/24	1	NM_000276.4	ENSP00000360154.4
OCRL	ENST00000357121.5	c.21C>T	p.Val7Val	synonymous_variant	1/23	1		ENSP00000349635.5
OCRL	ENST00000691455.1	n.21C>T		non_coding_transcript_exon_variant	1/18			ENSP00000510265.1
OCRL	ENST00000486673.1	n.91+521C>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.74e-7 AC: 1 AN: 1027044 Hom.: 0 Cov.: 31 AF XY: 0.00000302 AC XY: 1 AN XY: 331186

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: 0.00000124

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

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

Dec 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
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)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-128674437;