12-76358784-G-T

Position:

• chr12-76358784-G-T

Variant summary

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

The NM_020841.5(OSBPL8):​c.2356C>A​(p.Pro786Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 31)
• Consequence: OSBPL8 NM_020841.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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]

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=0.08802724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL8	NM_020841.5	c.2356C>A	p.Pro786Thr	missense_variant	22/24	ENST00000261183.8	NP_065892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL8	ENST00000261183.8	c.2356C>A	p.Pro786Thr	missense_variant	22/24	1	NM_020841.5	ENSP00000261183.3
OSBPL8	ENST00000393249.6	c.2230C>A	p.Pro744Thr	missense_variant	24/26	1		ENSP00000376939.2
OSBPL8	ENST00000611266.4	c.2230C>A	p.Pro744Thr	missense_variant	22/24	1		ENSP00000478240.1
OSBPL8	ENST00000393250.8	c.2230C>A	p.Pro744Thr	missense_variant	21/23	5		ENSP00000376940.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.2356C>A (p.P786T) alteration is located in exon 22 (coding exon 21) of the OSBPL8 gene. This alteration results from a C to A substitution at nucleotide position 2356, causing the proline (P) at amino acid position 786 to be replaced by a threonine (T). 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	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;T;.;.
Eigen	Benign	-0.070
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T;T;.
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.82	N;N;.;N
REVEL	Benign	0.023
Sift	Benign	0.36	T;T;.;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.13	.;B;.;.
Vest4		0.24
MutPred		0.25		.;Gain of phosphorylation at P786 (P = 0.0188);.;.;
MVP		0.20
MPC		0.47
ClinPred		0.35	T
GERP RS		5.9
Varity_R		0.059
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-76752564;