rs942617462

Variant names:

• chr7-24830802-C-A
• rs942617462
• NM_015550.4:c.1850G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-24830802-C-A
• chr7-24830802-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015550.4(OSBPL3):​c.1850G>T​(p.Arg617Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R617Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL3 NM_015550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL3	NM_015550.4	c.1850G>T	p.Arg617Leu	missense_variant	Exon 16 of 23	ENST00000313367.7	NP_056365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL3	ENST00000313367.7	c.1850G>T	p.Arg617Leu	missense_variant	Exon 16 of 23	1	NM_015550.4	ENSP00000315410.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.1	M;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.7	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.98	D;P;P;P
Vest4		0.79
MutPred		0.70		Loss of sheet (P = 0.0315);.;.;.;
MVP		0.66
MPC		0.87
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.92
gMVP		0.77

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

Other links and lift over

dbSNP: rs942617462; hg19: chr7-24870421;