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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 made for transcript

Verdict is Uncertain_significance. Variant got 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.:

GnomAD3 exomes

AF:

0.00000897

AC:

AN:

223058

Hom.:

AF XY:

0.00000836

AC XY:

AN XY:

119568

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

Cov.:

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over