chr7-24804379-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015550.4(OSBPL3):c.2503C>G(p.Leu835Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
OSBPL3
NM_015550.4 missense
NM_015550.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.32
Genes affected
OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) 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. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04139453).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OSBPL3 | NM_015550.4 | c.2503C>G | p.Leu835Val | missense_variant | 22/23 | ENST00000313367.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OSBPL3 | ENST00000313367.7 | c.2503C>G | p.Leu835Val | missense_variant | 22/23 | 1 | NM_015550.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152116Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000107 AC: 27AN: 251340Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135840
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461790Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727198
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.2503C>G (p.L835V) alteration is located in exon 22 (coding exon 21) of the OSBPL3 gene. This alteration results from a C to G substitution at nucleotide position 2503, causing the leucine (L) at amino acid position 835 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
P;B;B;B
Vest4
MutPred
Gain of MoRF binding (P = 0.0863);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at