3-31668759-T-C

Position:

• chr3-31668759-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL10	NM_017784.5	c.1979A>G	p.Asn660Ser	missense_variant	10/12	ENST00000396556.7	NP_060254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL10	ENST00000396556.7	c.1979A>G	p.Asn660Ser	missense_variant	10/12	1	NM_017784.5	ENSP00000379804.2
OSBPL10	ENST00000438237.6	c.1787A>G	p.Asn596Ser	missense_variant	9/11	2		ENSP00000406124.2
OSBPL10	ENST00000429492.6	c.1283A>G	p.Asn428Ser	missense_variant	7/8	2		ENSP00000416078.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.1979A>G (p.N660S) alteration is located in exon 10 (coding exon 10) of the OSBPL10 gene. This alteration results from a A to G substitution at nucleotide position 1979, causing the asparagine (N) at amino acid position 660 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.35
Sift	Benign	0.067	T;T
Sift4G	Benign	0.067	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1700258703; hg19: chr3-31710251; COSMIC: COSV67339811; COSMIC: COSV67339811;