NM_016540.4:c.662G>C

Variant names:

• chr11-94380759-C-G
• rs149566608
• NM_016540.4:c.662G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016540.4(GPR83):​c.662G>C​(p.Arg221Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R221H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.56
• Publications: 7 publications found

Genes affected

GPR83 (HGNC:4523): (G protein-coupled receptor 83) Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016540.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	NM_016540.4	MANE Select	c.662G>C	p.Arg221Pro	missense	Exon 4 of 4	NP_057624.3
	GPR83	NM_001330345.2		c.536G>C	p.Arg179Pro	missense	Exon 3 of 3	NP_001317274.1	Q9NYM4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	ENST00000243673.7	TSL:1 MANE Select	c.662G>C	p.Arg221Pro	missense	Exon 4 of 4	ENSP00000243673.2	Q9NYM4-1
	GPR83	ENST00000539203.2	TSL:5	c.536G>C	p.Arg179Pro	missense	Exon 3 of 3	ENSP00000441550.1	Q9NYM4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.035	D
Polyphen		0.46	P
Vest4		0.92
MutPred		0.66		Gain of glycosylation at S222 (P = 0.1198)
MVP		0.77
MPC		0.24
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.97
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149566608; hg19: chr11-94113925;