NM_017784.5:c.1537G>C

Variant names:

• chr3-31683823-C-G
• rs140782910
• NM_017784.5:c.1537G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017784.5(OSBPL10):​c.1537G>C​(p.Glu513Gln) 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. 16/22 in silico tools predict a benign 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. E513K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSBPL10 NM_017784.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 8 publications found

Genes affected

OSBPL10 (HGNC:16395): (oxysterol binding protein like 10) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12922454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017784.5. 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
	OSBPL10	NM_017784.5	MANE Select	c.1537G>C	p.Glu513Gln	missense	Exon 8 of 12	NP_060254.2
	OSBPL10	NM_001174060.2		c.1345G>C	p.Glu449Gln	missense	Exon 7 of 11	NP_001167531.1	Q9BXB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL10	ENST00000396556.7	TSL:1 MANE Select	c.1537G>C	p.Glu513Gln	missense	Exon 8 of 12	ENSP00000379804.2	Q9BXB5-1
	OSBPL10	ENST00000959571.1		c.1432G>C	p.Glu478Gln	missense	Exon 8 of 12	ENSP00000629630.1
	OSBPL10	ENST00000911816.1		c.1387G>C	p.Glu463Gln	missense	Exon 7 of 11	ENSP00000581875.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.87
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.13	N
PhyloP100		3.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.095
Sift	Benign	0.20	T
Sift4G	Benign	0.56	T
Polyphen		0.69	P
Vest4		0.096
MutPred		0.58		Loss of glycosylation at P508 (P = 0.0364)
MVP		0.41
MPC		0.26
ClinPred		0.19	T
GERP RS		2.8
Varity_R		0.047
gMVP		0.41
Mutation Taster		=100/0	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

dbSNP: rs140782910; hg19: chr3-31725315;