7-24809938-C-G

Variant names:

• chr7-24809938-C-G
• NM_015550.4:c.2186G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015550.4(OSBPL3):​c.2186G>C​(p.Ser729Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL3 NM_015550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3115429).

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.2186G>C	p.Ser729Thr	missense	Exon 20 of 23	NP_056365.1	Q9H4L5-1
	OSBPL3	NM_145320.2		c.2093G>C	p.Ser698Thr	missense	Exon 18 of 21	NP_663160.1	Q9H4L5-2
	OSBPL3	NM_145321.2		c.2078G>C	p.Ser693Thr	missense	Exon 18 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.2186G>C	p.Ser729Thr	missense	Exon 20 of 23	ENSP00000315410.2	Q9H4L5-1
	OSBPL3	ENST00000396431.5	TSL:1	c.2093G>C	p.Ser698Thr	missense	Exon 18 of 21	ENSP00000379708.1	Q9H4L5-2
	OSBPL3	ENST00000396429.5	TSL:1	c.2078G>C	p.Ser693Thr	missense	Exon 18 of 21	ENSP00000379706.1	Q9H4L5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.17
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.067	T
Polyphen		0.59	P
Vest4		0.30
MutPred		0.74		Loss of sheet (P = 0.1158)
MVP		0.56
MPC		0.39
ClinPred		0.80	D
GERP RS		4.4
Varity_R		0.70
gMVP		0.51
Mutation Taster		=90/10	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: chr7-24849557;