3-31664209-C-A

Variant names:

• chr3-31664209-C-A
• rs201507517
• NM_017784.5:c.2120G>T

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.2120G>T​(p.Arg707Leu) 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. R707Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL10 NM_017784.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 0 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=0.0994384).

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.2120G>T	p.Arg707Leu	missense	Exon 11 of 12	NP_060254.2
	OSBPL10	NM_001174060.2		c.1928G>T	p.Arg643Leu	missense	Exon 10 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.2120G>T	p.Arg707Leu	missense	Exon 11 of 12	ENSP00000379804.2	Q9BXB5-1
	OSBPL10	ENST00000959571.1		c.2015G>T	p.Arg672Leu	missense	Exon 11 of 12	ENSP00000629630.1
	OSBPL10	ENST00000911816.1		c.1970G>T	p.Arg657Leu	missense	Exon 10 of 11	ENSP00000581875.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.086
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.053
Sift	Benign	0.59	T
Sift4G	Benign	0.73	T
Polyphen		0.098	B
Vest4		0.33
MutPred		0.50		Gain of glycosylation at T706 (P = 0.0058)
MVP		0.39
MPC		0.45
ClinPred		0.39	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.50
Mutation Taster		=94/6	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: rs201507517; hg19: chr3-31705701;