X-129539976-AATATATAT-AATATATATATAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.025 (78 hom., 455 hem., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: 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-AATAT is Benign according to our data. Variant chrX-129539976-A-AATAT is described in ClinVar as Benign. ClinVar VariationId is 1274925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 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+38insATAT		intron	N/A
	OCRL	ENST00000927771.1		c.-464_-463insATAT		upstream_gene	N/A	ENSP00000597830.1
	OCRL	ENST00000851833.1		c.-464_-463insATAT		upstream_gene	N/A	ENSP00000521892.1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 2546 AN: 101629 Hom.: 78 Cov.: 16

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.00719

Gnomad FIN AF: 0.00275

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.0157

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: 0.0251 AC: 2546 AN: 101626 Hom.: 78 Cov.: 16 AF XY: 0.0171 AC XY: 455 AN XY: 26534

African (AFR) AF: 0.0837 AC: 2284 AN: 27304

American (AMR) AF: 0.0102 AC: 97 AN: 9517

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2507

East Asian (EAS) AF: 0.0122 AC: 38 AN: 3104

South Asian (SAS) AF: 0.00679 AC: 15 AN: 2210

European-Finnish (FIN) AF: 0.00275 AC: 12 AN: 4362

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

European-Non Finnish (NFE) AF: 0.00157 AC: 79 AN: 50413

Other (OTH) AF: 0.0156 AC: 21 AN: 1350

Alfa AF: 0.0000631 Hom.: 15

ClinVar

ClinVar submissions as Germline

Significance: 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;