X-129539976-AATATATAT-AATATATATATATATAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000486673.1(OCRL):​n.91+37_91+38insATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (10 hom., 95 hem., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant X-129539976-A-AATATATAT is Benign according to our data. Variant chrX-129539976-A-AATATATAT is described in ClinVar as Likely_benign. ClinVar VariationId is 1203012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00723 (735/101654) while in subpopulation EAS AF = 0.0483 (150/3104). AF 95% confidence interval is 0.042. There are 10 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

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+38insATATATAT		intron	N/A
	OCRL	ENST00000927771.1		c.-464_-463insATATATAT		upstream_gene	N/A	ENSP00000597830.1
	OCRL	ENST00000851833.1		c.-464_-463insATATATAT		upstream_gene	N/A	ENSP00000521892.1

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 736 AN: 101657 Hom.: 10 Cov.: 16

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.000399

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.00854

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000198

Gnomad OTH AF: 0.00824

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: 0.00723 AC: 735 AN: 101654 Hom.: 10 Cov.: 16 AF XY: 0.00358 AC XY: 95 AN XY: 26542

African (AFR) AF: 0.0126 AC: 344 AN: 27333

American (AMR) AF: 0.0209 AC: 199 AN: 9510

Ashkenazi Jewish (ASJ) AF: 0.000399 AC: 1 AN: 2507

East Asian (EAS) AF: 0.0483 AC: 150 AN: 3104

South Asian (SAS) AF: 0.00860 AC: 19 AN: 2210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.000198 AC: 10 AN: 50417

Other (OTH) AF: 0.00889 AC: 12 AN: 1350

Alfa AF: 0.00 Hom.: 15

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;