Variant 7-24800272-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015550.4(OSBPL3):c.2575G>A(p.Asp859Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,604,726 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 16 hom. )

Consequence

OSBPL3
NM_015550.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

OSBPL3 links:

OSBPL3 (HGNC:):

OSBPL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004227251).

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL3	NM_015550.4 linkuse as main transcript	c.2575G>A	p.Asp859Asn	missense_variant	23/23	ENST00000313367.7	NP_056365.1	Q9H4L5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL3	ENST00000313367.7 linkuse as main transcript	c.2575G>A	p.Asp859Asn	missense_variant	23/23	1	NM_015550.4	ENSP00000315410.2		Q9H4L5-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00290

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00124

AC:

311

AN:

250694

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00256

AC:

3723

AN:

1452518

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1818

AN XY:

723180

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00266

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152208

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00158

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00138

AC:

168

EpiCase

AF:

0.00289

EpiControl

AF:

0.00219

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

Aug 23, 2021

The c.2575G>A (p.D859N) alteration is located in exon 23 (coding exon 22) of the OSBPL3 gene. This alteration results from a G to A substitution at nucleotide position 2575, causing the aspartic acid (D) at amino acid position 859 to be replaced by an asparagine (N). 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

0.059

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.13

DANN

Benign

0.69

DEOGEN2

Benign

0.021

T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.18

T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.34

N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.51

T;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.12

MVP

0.15

MPC

0.21

ClinPred

0.0025

GERP RS

-11

Varity_R

0.035

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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