X-129575158-C-G

Variant names:

• chrX-129575158-C-G
• NM_000276.4:c.1621C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000276.4(OCRL):​c.1621C>G​(p.Arg541Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,090,371 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: OCRL NM_000276.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23688233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCRL	NM_000276.4	c.1621C>G	p.Arg541Gly	missense_variant	Exon 16 of 24	ENST00000371113.9	NP_000267.2
OCRL	NM_001318784.2	c.1624C>G	p.Arg542Gly	missense_variant	Exon 16 of 24		NP_001305713.1
OCRL	NM_001587.4	c.1621C>G	p.Arg541Gly	missense_variant	Exon 16 of 23		NP_001578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCRL	ENST00000371113.9	c.1621C>G	p.Arg541Gly	missense_variant	Exon 16 of 24	1	NM_000276.4	ENSP00000360154.4
OCRL	ENST00000357121.5	c.1621C>G	p.Arg541Gly	missense_variant	Exon 16 of 23	1		ENSP00000349635.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1090371 Hom.: 0 Cov.: 27 AF XY: 0.00000281 AC XY: 1 AN XY: 356301

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000359

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.28
Sift	Benign	0.072	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0030	B;B
Vest4		0.29
MutPred		0.56		Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);
MVP		0.82
MPC		1.4
ClinPred		0.37	T
GERP RS		3.0
Varity_R		0.42
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-128709135;