dbSNP rs927830660: OSBPL6:p.Ser45Cys (chr2-178324208-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032523.4(OSBPL6):c.134C>G(p.Ser45Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,429,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S45F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

OSBPL6
NM_032523.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09

Publications

1 publications found

Variant links:

Genes affected

OSBPL6 (HGNC:16388): (oxysterol binding protein like 6) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OSBPL6 links:

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ACMG classification

Classification was made for transcript

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=0.10874769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL6	NM_032523.4 link	c.134C>G	p.Ser45Cys	missense_variant	Exon 4 of 25	ENST00000190611.9	NP_115912.1	Q9BZF3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL6	ENST00000190611.9 link	c.134C>G	p.Ser45Cys	missense_variant	Exon 4 of 25	1	NM_032523.4	ENSP00000190611.4		Q9BZF3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000897

AC:

AN:

223058

AF XY:

0.00000836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000350

AC:

AN:

1429188

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33106

American (AMR)

AF:

0.0000693

AC:

AN:

43264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25370

East Asian (EAS)

AF:

0.00

AC:

AN:

39052

South Asian (SAS)

AF:

0.00

AC:

AN:

82398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089718

Other (OTH)

AF:

0.0000340

AC:

AN:

58864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

.;.;.;.;T;.;.

Eigen

Benign

0.038

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D;D;D;.;D

M_CAP

Benign

0.0032

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.26

N;N;N;N;N;N;.

PhyloP100

3.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0020

D;D;D;D;D;D;D

Sift4G

Benign

0.068

T;T;T;T;T;T;D

Polyphen

0.30

B;B;.;B;B;B;P

Vest4

0.38

MutPred

0.18

Loss of phosphorylation at S45 (P = 0.0123);Loss of phosphorylation at S45 (P = 0.0123);Loss of phosphorylation at S45 (P = 0.0123);Loss of phosphorylation at S45 (P = 0.0123);Loss of phosphorylation at S45 (P = 0.0123);Loss of phosphorylation at S45 (P = 0.0123);.;

MVP

0.068

MPC

0.40

ClinPred

0.33

GERP RS

6.0

Varity_R

0.14

gMVP

0.37

Mutation Taster

=88/12

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over