X-129539976-AATATATAT-AATATATATAT

Variant names:

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

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+38insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (197 hom., 1031 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-AAT is Benign according to our data. Variant chrX-129539976-A-AAT is described in ClinVar as Benign. ClinVar VariationId is 1258378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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+38insAT		intron	N/A
	OCRL	ENST00000927771.1		c.-464_-463insAT		upstream_gene	N/A	ENSP00000597830.1
	OCRL	ENST00000851833.1		c.-464_-463insAT		upstream_gene	N/A	ENSP00000521892.1

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 5285 AN: 101574 Hom.: 197 Cov.: 16

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0298

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0489

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0540

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: 0.0520 AC: 5285 AN: 101571 Hom.: 197 Cov.: 16 AF XY: 0.0389 AC XY: 1031 AN XY: 26503

African (AFR) AF: 0.128 AC: 3485 AN: 27318

American (AMR) AF: 0.0321 AC: 305 AN: 9512

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 47 AN: 2507

East Asian (EAS) AF: 0.0296 AC: 92 AN: 3105

South Asian (SAS) AF: 0.0481 AC: 106 AN: 2206

European-Finnish (FIN) AF: 0.0166 AC: 72 AN: 4341

Middle Eastern (MID) AF: 0.0392 AC: 8 AN: 204

European-Non Finnish (NFE) AF: 0.0218 AC: 1098 AN: 50376

Other (OTH) AF: 0.0534 AC: 72 AN: 1348

Alfa AF: 0.00417 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;