chr19-54095883-A-G

Position:

• chr19-54095883-A-G

Variant summary

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

The NM_133169.6(OSCAR):​c.644T>C​(p.Ile215Thr) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSCAR NM_133169.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.894

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=0.25037897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSCAR	NM_133169.6	c.644T>C	p.Ile215Thr	missense_variant	4/5	ENST00000358375.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSCAR	ENST00000358375.9	c.644T>C	p.Ile215Thr	missense_variant	4/5	1	NM_133169.6	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 22, 2022

The c.656T>C (p.I219T) alteration is located in exon 5 (coding exon 5) of the OSCAR gene. This alteration results from a T to C substitution at nucleotide position 656, causing the isoleucine (I) at amino acid position 219 to be replaced by a threonine (T). 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	Pathogenic	0.97
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;.;.;.;T;T;.;.;.;.
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.67	.;.;T;.;T;T;T;.;T;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	D;N;N;N;N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N;N;.;N;N;N;.;.;.;N
REVEL	Benign	0.18
Sift	Benign	0.030	D;D;.;D;D;D;.;.;.;D
Sift4G	Uncertain	0.012	D;T;T;D;T;T;T;D;D;D
Vest4		0.48
MutPred		0.63		.;.;.;.;Gain of glycosylation at I215 (P = 0.0062);.;.;.;.;Gain of glycosylation at I215 (P = 0.0062);
MVP		0.40
MPC		1.2
ClinPred		0.90	D
GERP RS		3.9
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54599148;