19-54095968-C-A

Position:

• chr19-54095968-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133169.6(OSCAR):​c.559G>T​(p.Ala187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,437,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: OSCAR NM_133169.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.249

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 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=0.03183773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSCAR	NM_133169.6	c.559G>T	p.Ala187Ser	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.559G>T	p.Ala187Ser	missense_variant	4/5	1	NM_133169.6	ENSP00000351145.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1437260 Hom.: 0 Cov.: 32 AF XY: 0.00000561 AC XY: 4 AN XY: 712784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000739

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000252 AC: 3

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

Oct 07, 2024

The c.571G>T (p.A191S) alteration is located in exon 5 (coding exon 5) of the OSCAR gene. This alteration results from a G to T substitution at nucleotide position 571, causing the alanine (A) at amino acid position 191 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.87
DEOGEN2	Benign	0.019	.;.;.;.;T;T;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.58	.;.;T;.;T;T;T;.;T;.
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.032	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.81	N;N;.;N;N;N;.;.;.;N
REVEL	Benign	0.025
Sift	Benign	1.0	T;T;.;T;T;T;.;.;.;T
Sift4G	Benign	0.25	T;T;T;T;T;T;T;T;T;T
Vest4		0.051
MutPred		0.47		.;.;.;.;Gain of glycosylation at A187 (P = 0.0102);.;.;.;.;Gain of glycosylation at A187 (P = 0.0102);
MVP		0.043
MPC		0.39
ClinPred		0.13	T
GERP RS		-3.4
gMVP		0.20

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

Other links and lift over

dbSNP: rs745645597; hg19: chr19-54599233;