X-129539976-A-AATATATAT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCRL	ENST00000486673.1	n.91+37_91+38insATATATAT		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 736 AN: 101657 Hom.: 10 Cov.: 16 AF XY: 0.00358 AC XY: 95 AN XY: 26531

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00723 AC: 735 AN: 101654 Hom.: 10 Cov.: 16 AF XY: 0.00358 AC XY: 95 AN XY: 26542

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.000399

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.00860

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000198

Gnomad4 OTH AF: 0.00889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 19, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs766806372; hg19: chrX-128673953;