12-76394680-C-T

Position:

• chr12-76394680-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020841.5(OSBPL8):​c.722G>A​(p.Ser241Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL8 NM_020841.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

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 (HGNC:):

ACMG classification

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=0.37094566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL8	NM_020841.5	c.722G>A	p.Ser241Asn	missense_variant	9/24	ENST00000261183.8	NP_065892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL8	ENST00000261183.8	c.722G>A	p.Ser241Asn	missense_variant	9/24	1	NM_020841.5	ENSP00000261183.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 05, 2022

The c.722G>A (p.S241N) alteration is located in exon 9 (coding exon 8) of the OSBPL8 gene. This alteration results from a G to A substitution at nucleotide position 722, causing the serine (S) at amino acid position 241 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	.;D;.;.;D;D
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;.;D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.37	T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N;N;.;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.094	T;T;.;T;T;T
Sift4G	Benign	0.13	T;T;T;T;.;.
Polyphen		0.031, 0.0070	.;B;.;.;.;B
Vest4		0.33
MutPred		0.47		.;Gain of catalytic residue at Y242 (P = 0);.;.;Gain of catalytic residue at Y242 (P = 0);.;
MVP		0.43
MPC		2.5
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.68

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: chr12-76788460;