12-54362938-C-G

Position:

• chr12-54362938-C-G

Variant summary

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

The NM_020370.3(GPR84):​c.914G>C​(p.Arg305Thr) 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. 14/21 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: GPR84 NM_020370.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.84

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 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=0.049764574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR84	NM_020370.3	c.914G>C	p.Arg305Thr	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.914G>C	p.Arg305Thr	missense_variant	2/2	1	NM_020370.3	ENSP00000267015.3
GPR84	ENST00000551809.1	c.914G>C	p.Arg305Thr	missense_variant	1/1	6		ENSP00000450310.1
GPR84-AS1	ENST00000550474.5	n.47+9231C>G		intron_variant		4
GPR84-AS1	ENST00000552785.1	n.105+9042C>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jun 29, 2023

The c.914G>C (p.R305T) alteration is located in exon 2 (coding exon 1) of the GPR84 gene. This alteration results from a G to C substitution at nucleotide position 914, causing the arginine (R) at amino acid position 305 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	Benign	0.093
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0030
DANN	Benign	0.62
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.010
Sift	Benign	0.20	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0090	B;B
Vest4		0.11
MutPred		0.47		Gain of glycosylation at R305 (P = 0.0012);Gain of glycosylation at R305 (P = 0.0012);
MVP		0.16
MPC		0.23
ClinPred		0.12	T
GERP RS		-6.1
Varity_R		0.044
gMVP		0.22

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: rs1954286850; hg19: chr12-54756722; COSMIC: COSV57209296;