Variant 11-3088269-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020896.4(OSBPL5):c.2576G>A(p.Arg859Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

OSBPL5
NM_020896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

OSBPL5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28442925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL5	NM_020896.4 link	c.2576G>A	p.Arg859Gln	missense_variant	22/22	ENST00000263650.12	NP_065947.1	Q9H0X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12 link	c.2576G>A	p.Arg859Gln	missense_variant	22/22	1	NM_020896.4	ENSP00000263650.7		Q9H0X9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000817

AC:

AN:

244878

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456404

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.2576G>A (p.R859Q) alteration is located in exon 22 (coding exon 21) of the OSBPL5 gene. This alteration results from a G to A substitution at nucleotide position 2576, causing the arginine (R) at amino acid position 859 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0084

.;T;.;T;.;.

Eigen

Benign

0.080

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.86

D;D;.;D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

.;M;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.032

D;D;D;D;D;D

Sift4G

Uncertain

0.027

D;T;T;T;D;T

Polyphen

0.95

.;P;.;.;.;.

Vest4

0.42

MutPred

0.44

.;Loss of glycosylation at P858 (P = 0.1193);.;.;.;.;

MVP

0.52

MPC

0.44

ClinPred

0.74

GERP RS

3.9

Varity_R

0.059

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over