NM_017784.5:c.1979A>G

Variant names:

• chr3-31668759-T-C
• rs1700258703
• NM_017784.5:c.1979A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017784.5(OSBPL10):​c.1979A>G​(p.Asn660Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: OSBPL10 NM_017784.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

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.1979A>G	p.Asn660Ser	missense	Exon 10 of 12	NP_060254.2
	OSBPL10	NM_001174060.2		c.1787A>G	p.Asn596Ser	missense	Exon 9 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.1979A>G	p.Asn660Ser	missense	Exon 10 of 12	ENSP00000379804.2	Q9BXB5-1
	OSBPL10	ENST00000959571.1		c.1874A>G	p.Asn625Ser	missense	Exon 10 of 12	ENSP00000629630.1
	OSBPL10	ENST00000911816.1		c.1829A>G	p.Asn610Ser	missense	Exon 9 of 11	ENSP00000581875.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

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	0.28
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.35
Sift	Benign	0.067	T
Sift4G	Benign	0.067	T
Polyphen		0.99	D
Vest4		0.89
MutPred		0.53		Gain of sheet (P = 0.1539)
MVP		0.70
MPC		0.73
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.80
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1700258703; hg19: chr3-31710251; COSMIC: COSV67339811; COSMIC: COSV67339811;