19-54096099-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_133169.6(OSCAR):c.428G>A(p.Gly143Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
OSCAR
NM_133169.6 missense
NM_133169.6 missense
Scores
3
2
12
Clinical Significance
Conservation
PhyloP100: -0.0600
Genes affected
OSCAR (HGNC:29960): (osteoclast associated Ig-like receptor) Osteoclasts are multinucleated cells that resorb bone and are essential for bone homeostasis. This gene encodes an osteoclast-associated receptor (OSCAR), which is a member of the leukocyte receptor complex protein family that plays critical roles in the regulation of both innate and adaptive immune responses. The encoded protein may play a role in oxidative stress-mediated atherogenesis as well as monocyte adhesion. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.755
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSCAR | NM_133169.6 | c.428G>A | p.Gly143Asp | missense_variant | 4/5 | ENST00000358375.9 | NP_573399.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSCAR | ENST00000358375.9 | c.428G>A | p.Gly143Asp | missense_variant | 4/5 | 1 | NM_133169.6 | ENSP00000351145.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1378748Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 680392
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296
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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 | Aug 13, 2021 | The c.440G>A (p.G147D) alteration is located in exon 5 (coding exon 5) of the OSCAR gene. This alteration results from a G to A substitution at nucleotide position 440, causing the glycine (G) at amino acid position 147 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
.;.;.;.;T;T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;.;T;T;T;.;T;.
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D;D;D;.;.;.;D
REVEL
Benign
Sift
Uncertain
D;D;.;D;D;D;.;.;.;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T
Vest4
MutPred
0.88
.;.;.;.;Loss of MoRF binding (P = 0.0536);.;.;.;.;Loss of MoRF binding (P = 0.0536);
MVP
MPC
1.2
ClinPred
D
GERP RS
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