chr7-24806849-C-T

Variant names:

• chr7-24806849-C-T
• NM_015550.4:c.2371G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015550.4(OSBPL3):​c.2371G>A​(p.Glu791Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSBPL3 NM_015550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL3	NM_015550.4	MANE Select	c.2371G>A	p.Glu791Lys	missense	Exon 21 of 23	NP_056365.1	Q9H4L5-1
	OSBPL3	NM_145320.2		c.2278G>A	p.Glu760Lys	missense	Exon 19 of 21	NP_663160.1	Q9H4L5-2
	OSBPL3	NM_145321.2		c.2263G>A	p.Glu755Lys	missense	Exon 19 of 21	NP_663161.1	Q9H4L5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL3	ENST00000313367.7	TSL:1 MANE Select	c.2371G>A	p.Glu791Lys	missense	Exon 21 of 23	ENSP00000315410.2	Q9H4L5-1
	OSBPL3	ENST00000396431.5	TSL:1	c.2278G>A	p.Glu760Lys	missense	Exon 19 of 21	ENSP00000379708.1	Q9H4L5-2
	OSBPL3	ENST00000396429.5	TSL:1	c.2263G>A	p.Glu755Lys	missense	Exon 19 of 21	ENSP00000379706.1	Q9H4L5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.97	D
Vest4		0.76
MutPred		0.58		Gain of methylation at E791 (P = 0.0082)
MVP		0.68
MPC		0.68
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.77
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr7-24846468;