19-54096069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133169.6(OSCAR):​c.458G>A​(p.Arg153His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,539,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

OSCAR
NM_133169.6 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200
Variant links:
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]

Genome browser will be placed here

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=0.104839146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSCARNM_133169.6 linkuse as main transcriptc.458G>A p.Arg153His missense_variant 4/5 ENST00000358375.9 NP_573399.2 Q8IYS5A0A0A0MRF2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSCARENST00000358375.9 linkuse as main transcriptc.458G>A p.Arg153His missense_variant 4/51 NM_133169.6 ENSP00000351145.4 A0A0A0MRF2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.21e-7
AC:
1
AN:
1387210
Hom.:
0
Cov.:
32
AF XY:
0.00000146
AC XY:
1
AN XY:
685078
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.26e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000105
AC:
1

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 submitterclinical testingAmbry GeneticsDec 14, 2021The c.470G>A (p.R157H) 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 470, causing the arginine (R) at amino acid position 157 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
.;.;.;.;T;T;.;.;.;.
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.068
N
LIST_S2
Benign
0.79
.;.;T;.;T;T;T;.;T;.
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.10
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.4
N;N;.;N;N;N;.;.;.;N
REVEL
Benign
0.048
Sift
Benign
0.038
D;T;.;D;T;T;.;.;.;D
Sift4G
Benign
0.16
T;D;D;T;D;T;D;T;T;T
Vest4
0.22
MutPred
0.47
.;.;.;.;Loss of MoRF binding (P = 0.0117);.;.;.;.;Loss of MoRF binding (P = 0.0117);
MVP
0.043
MPC
0.49
ClinPred
0.51
D
GERP RS
-3.6
gMVP
0.24

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.

Other links and lift over

dbSNP: rs748233554; hg19: chr19-54599334; API