Variant 12-76402708-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020841.5(OSBPL8):c.347C>G(p.Thr116Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,604,792 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: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OSBPL8
NM_020841.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.72

Variant links:

Genes affected

OSBPL8 (HGNC:16396): (oxysterol binding protein like 8) This gene encodes a member of a family of proteins containing an N-terminal pleckstrin homology domain and a highly conserved C-terminal oxysterol-binding protein-like sterol-binding domain. It binds mutliple lipid-containing molecules, including phosphatidylserine, phosphatidylinositol 4-phosphate (PI4P) and oxysterol, and promotes their exchange between the endoplasmic reticulum and the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

OSBPL8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33760113).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL8	NM_020841.5 linkuse as main transcript	c.347C>G	p.Thr116Arg	missense_variant	6/24	ENST00000261183.8	NP_065892.1	Q9BZF1-1A0A024RBB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL8	ENST00000261183.8 linkuse as main transcript	c.347C>G	p.Thr116Arg	missense_variant	6/24	1	NM_020841.5	ENSP00000261183.3		Q9BZF1-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249696

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1452876

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723312

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.0000451

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000112

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ExAC

AF:

0.0000247

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

Feb 27, 2024

The c.347C>G (p.T116R) alteration is located in exon 6 (coding exon 5) of the OSBPL8 gene. This alteration results from a C to G substitution at nucleotide position 347, causing the threonine (T) at amino acid position 116 to be replaced by an arginine (R). 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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T;.;.;T;T;T;T;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D;D;.;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.34

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.1

.;M;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.4

N;N;.;N;N;N;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0070

D;D;.;D;D;D;D;D;D

Sift4G

Benign

0.062

T;D;T;T;.;.;D;.;.

Polyphen

1.0, 0.99

.;D;.;.;.;D;.;.;.

Vest4

0.68

MutPred

0.20

.;Gain of helix (P = 0.0164);.;.;Gain of helix (P = 0.0164);.;.;.;.;

MVP

0.26

MPC

1.0

ClinPred

0.33

GERP RS

5.9

Varity_R

0.31

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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