chr19-54096927-C-A

Position:

• chr19-54096927-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133169.6(OSCAR):​c.308G>T​(p.Arg103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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. R103Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: OSCAR NM_133169.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.577

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]

ACMG classification

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=0.12963024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSCAR	NM_133169.6	c.308G>T	p.Arg103Leu	missense_variant	3/5	ENST00000358375.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSCAR	ENST00000358375.9	c.308G>T	p.Arg103Leu	missense_variant	3/5	1	NM_133169.6	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.320G>T (p.R107L) alteration is located in exon 4 (coding exon 4) of the OSCAR gene. This alteration results from a G to T substitution at nucleotide position 320, causing the arginine (R) at amino acid position 107 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.6
DANN	Benign	0.83
DEOGEN2	Benign	0.033	.;.;.;.;T;T;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.64	.;.;T;.;T;T;T;.;T;.
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N;N;.;D;N;N;.;.;.;N
REVEL	Benign	0.088
Sift	Benign	0.16	T;T;.;T;T;T;.;.;.;T
Sift4G	Benign	0.43	T;T;T;T;T;T;T;T;T;T
Vest4		0.23
MutPred		0.59		.;.;.;.;Loss of catalytic residue at R103 (P = 0.0342);.;.;.;.;Loss of catalytic residue at R103 (P = 0.0342);
MVP		0.28
MPC		0.64
ClinPred		0.22	T
GERP RS		-4.2
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54600214; COSMIC: COSV52928522;