X-129539976-AATATATAT-AATATATATATATAT

Variant names:

• chrX-129539976-A-AATATAT
• rs766806372
• ENST00000486673.1:n.91+37_91+38insATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000486673.1(OCRL):​n.91+37_91+38insATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (95 hom., 493 hem., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• 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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• oculocerebrorenal syndrome

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486673.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCRL	ENST00000486673.1	TSL:5	n.91+37_91+38insATATAT		intron	N/A
	OCRL	ENST00000927771.1		c.-464_-463insATATAT		upstream_gene	N/A	ENSP00000597830.1
	OCRL	ENST00000851833.1		c.-464_-463insATATAT		upstream_gene	N/A	ENSP00000521892.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 2471 AN: 101642 Hom.: 96 Cov.: 16

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0172

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.00802

Gnomad MID AF: 0.0178

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0262

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AF: 0.00 AC: 0 AN: 1

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 15

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0242 AC: 2464 AN: 101640 Hom.: 95 Cov.: 16 AF XY: 0.0186 AC XY: 493 AN XY: 26536

African (AFR) AF: 0.0209 AC: 570 AN: 27336

American (AMR) AF: 0.0377 AC: 358 AN: 9501

Ashkenazi Jewish (ASJ) AF: 0.0172 AC: 43 AN: 2507

East Asian (EAS) AF: 0.225 AC: 698 AN: 3104

South Asian (SAS) AF: 0.0883 AC: 195 AN: 2208

European-Finnish (FIN) AF: 0.00802 AC: 35 AN: 4363

Middle Eastern (MID) AF: 0.00980 AC: 2 AN: 204

European-Non Finnish (NFE) AF: 0.0105 AC: 528 AN: 50412

Other (OTH) AF: 0.0259 AC: 35 AN: 1350

Alfa AF: 0.00265 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061

Splicing

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

Other links and lift over

dbSNP: rs766806372; hg19: chrX-128673953; COSMIC: COSV63980300;