X-129539986-TA-T

Position:

• chrX-129539986-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000486673.1(OCRL):​n.91+48delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 109,322 control chromosomes in the GnomAD database, including 2 homozygotes. There are 133 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., 133 hem., cov: 21)
  • Exomes 𝑓: 0.0028 (0 hom. 0 hem.)
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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-129539986-TA-T is Benign according to our data. Variant chrX-129539986-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1205397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00452 (493/108967) while in subpopulation AFR AF= 0.0148 (442/29899). AF 95% confidence interval is 0.0136. There are 2 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCRL	ENST00000486673.1	n.91+48delA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 492 AN: 108966 Hom.: 2 Cov.: 21 AF XY: 0.00419 AC XY: 132 AN XY: 31498

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00390

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00686

GnomAD4 exome AF: 0.00282 AC: 1 AN: 355 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 77

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00452 AC: 493 AN: 108967 Hom.: 2 Cov.: 21 AF XY: 0.00422 AC XY: 133 AN XY: 31515

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00390

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000190

Gnomad4 OTH AF: 0.00679

Alfa AF: 0.000644 Hom.: 2

Bravo AF: 0.00565

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2020

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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: rs903954464; hg19: chrX-128673963;