rs924766896

Variant names:

• chrX-129540468-A-T
• rs924766896
• NM_000276.4:c.29A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000276.4(OCRL):​c.29A>T​(p.Gln10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OCRL NM_000276.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31008816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000276.4. 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
	OCRL	NM_000276.4	MANE Select	c.29A>T	p.Gln10Leu	missense	Exon 1 of 24	NP_000267.2
	OCRL	NM_001318784.2		c.29A>T	p.Gln10Leu	missense	Exon 1 of 24	NP_001305713.1
	OCRL	NM_001587.4		c.29A>T	p.Gln10Leu	missense	Exon 1 of 23	NP_001578.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCRL	ENST00000371113.9	TSL:1 MANE Select	c.29A>T	p.Gln10Leu	missense	Exon 1 of 24	ENSP00000360154.4	Q01968-1
	OCRL	ENST00000357121.5	TSL:1	c.29A>T	p.Gln10Leu	missense	Exon 1 of 23	ENSP00000349635.5	Q01968-2
	OCRL	ENST00000949289.1		c.29A>T	p.Gln10Leu	missense	Exon 1 of 24	ENSP00000619348.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1019985 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 328261

African (AFR) AF: 0.00 AC: 0 AN: 24002

American (AMR) AF: 0.00 AC: 0 AN: 27131

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17678

East Asian (EAS) AF: 0.00 AC: 0 AN: 24766

South Asian (SAS) AF: 0.00 AC: 0 AN: 49504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2767

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804132

Other (OTH) AF: 0.00 AC: 0 AN: 42516

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Lowe syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.42	T
Polyphen		0.037	B
Vest4		0.35
MutPred		0.24		Loss of sheet (P = 0.0457)
MVP		0.93
MPC		0.26
ClinPred		0.32	T
GERP RS		2.6
PromoterAI		0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.40
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs924766896; hg19: chrX-128674445;