X-129540487-C-A

Variant names:

• chrX-129540487-C-A
• rs1261991452
• NM_000276.4:c.39+9C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000276.4(OCRL):​c.39+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 973,155 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000010 (0 hom. 1 hem.)
• Consequence: OCRL NM_000276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Dent disease type 2

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• oculocerebrorenal syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000276.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCRL	NM_000276.4	MANE Select	c.39+9C>A		intron	N/A	NP_000267.2
	OCRL	NM_001318784.2		c.39+9C>A		intron	N/A	NP_001305713.1
	OCRL	NM_001587.4		c.39+9C>A		intron	N/A	NP_001578.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCRL	ENST00000371113.9	TSL:1 MANE Select	c.39+9C>A		intron	N/A	ENSP00000360154.4	Q01968-1
	OCRL	ENST00000357121.5	TSL:1	c.39+9C>A		intron	N/A	ENSP00000349635.5	Q01968-2
	OCRL	ENST00000949289.1		c.39+9C>A		intron	N/A	ENSP00000619348.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.0000106 AC: 1 AN: 94657 AF XY: 0.0000291

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000103 AC: 1 AN: 973155 Hom.: 0 Cov.: 31 AF XY: 0.00000330 AC XY: 1 AN XY: 302965

African (AFR) AF: 0.00 AC: 0 AN: 22752

American (AMR) AF: 0.00 AC: 0 AN: 26107

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16564

East Asian (EAS) AF: 0.00 AC: 0 AN: 23123

South Asian (SAS) AF: 0.0000206 AC: 1 AN: 48633

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25199

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2555

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 768277

Other (OTH) AF: 0.00 AC: 0 AN: 39945

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.92
PhyloP100		1.1
PromoterAI		-0.13	Neutral

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

Other links and lift over

dbSNP: rs1261991452; hg19: chrX-128674464;