X-129540492-A-C

Position:

• chrX-129540492-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000276.4(OCRL):​c.39+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: OCRL NM_000276.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-129540492-A-C is Benign according to our data. Variant chrX-129540492-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2836129.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCRL	NM_000276.4	c.39+14A>C		intron_variant		ENST00000371113.9
OCRL	NM_001318784.2	c.39+14A>C		intron_variant
OCRL	NM_001587.4	c.39+14A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCRL	ENST00000371113.9	c.39+14A>C		intron_variant		1	NM_000276.4	P1
OCRL	ENST00000357121.5	c.39+14A>C		intron_variant		1
OCRL	ENST00000691455.1	c.39+14A>C		intron_variant, NMD_transcript_variant
OCRL	ENST00000486673.1	n.91+553A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 19

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

Feb 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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-128674469;