chr12-54362842-A-G

Position:

• chr12-54362842-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020370.3(GPR84):​c.1010T>C​(p.Leu337Pro) 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: 6.59

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR84	NM_020370.3	c.1010T>C	p.Leu337Pro	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.1010T>C	p.Leu337Pro	missense_variant	2/2	1	NM_020370.3	ENSP00000267015.3
GPR84	ENST00000551809.1	c.1010T>C	p.Leu337Pro	missense_variant	1/1	6		ENSP00000450310.1
GPR84-AS1	ENST00000550474.5	n.47+9135A>G		intron_variant		4
GPR84-AS1	ENST00000552785.1	n.105+8946A>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

Jan 29, 2024

The c.1010T>C (p.L337P) 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 1010, causing the leucine (L) at amino acid position 337 to be replaced by a proline (P). 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	0.82
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.94	P;P
Vest4		0.86
MutPred		0.82		Loss of stability (P = 0.0139);Loss of stability (P = 0.0139);
MVP		0.83
MPC		0.83
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.89
gMVP		0.72

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: chr12-54756626;