12-54363356-A-G

Position:

• chr12-54363356-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020370.3(GPR84):​c.496T>C​(p.Cys166Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR84 NM_020370.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48

Genes affected

GPR84 (HGNC:4535): (G protein-coupled receptor 84) Predicted to enable urotensin II receptor activity. Predicted to be involved in neuropeptide signaling pathway. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

GPR84-AS1 (HGNC:):

ACMG classification

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, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR84	NM_020370.3	c.496T>C	p.Cys166Arg	missense_variant	2/2	ENST00000267015.4	NP_065103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR84	ENST00000267015.4	c.496T>C	p.Cys166Arg	missense_variant	2/2	1	NM_020370.3	ENSP00000267015.3
GPR84	ENST00000551809.1	c.496T>C	p.Cys166Arg	missense_variant	1/1	6		ENSP00000450310.1
GPR84-AS1	ENST00000550474.5	n.47+9649A>G		intron_variant		4
GPR84-AS1	ENST00000552785.1	n.105+9460A>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 21, 2024

The c.496T>C (p.C166R) alteration is located in exon 2 (coding exon 1) of the GPR84 gene. This alteration results from a T to C substitution at nucleotide position 496, causing the cysteine (C) at amino acid position 166 to be replaced by an arginine (R). 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	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.011	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.69		Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);
MVP		0.44
MPC		0.86
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.69
gMVP		0.74

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: chr12-54757140;