rs1935838755

Variant names:

• chr3-125547571-T-C
• rs1935838755
• NM_022776.5:c.1676A>G

Variant summary

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

The NM_022776.5(OSBPL11):​c.1676A>G​(p.His559Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL11 NM_022776.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12
• Publications: 0 publications found

Genes affected

OSBPL11 (HGNC:16397): (oxysterol binding protein like 11) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022776.5. 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
	OSBPL11	NM_022776.5	MANE Select	c.1676A>G	p.His559Arg	missense	Exon 10 of 13	NP_073613.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL11	ENST00000296220.6	TSL:1 MANE Select	c.1676A>G	p.His559Arg	missense	Exon 10 of 13	ENSP00000296220.5	Q9BXB4
	OSBPL11	ENST00000910157.1		c.1673A>G	p.His558Arg	missense	Exon 10 of 13	ENSP00000580216.1
	OSBPL11	ENST00000931704.1		c.1670A>G	p.His557Arg	missense	Exon 10 of 13	ENSP00000601763.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.22
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.43	N
PhyloP100		6.1
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.37
Sift	Benign	0.055	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.45		Gain of sheet (P = 0.1208)
MVP		0.46
MPC		1.1
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.61
gMVP		0.76
Mutation Taster		=29/71	disease causing

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: rs1935838755; hg19: chr3-125266415;