NM_004224.3:c.168C>G

Variant names:

• chrX-151176889-C-G
• rs1246151000
• NM_004224.3:c.168C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004224.3(GPR50):​c.168C>G​(p.Asn56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000367 in 1,090,133 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

Genes affected

GPR50 (HGNC:4506): (G protein-coupled receptor 50) This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

GPR50-AS1 (HGNC:40259): (GPR50 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004224.3. 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
	GPR50	NM_004224.3	MANE Select	c.168C>G	p.Asn56Lys	missense	Exon 1 of 2	NP_004215.2	Q13585
	GPR50-AS1	NR_135300.1		n.461-14G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	ENST00000218316.4	TSL:1 MANE Select	c.168C>G	p.Asn56Lys	missense	Exon 1 of 2	ENSP00000218316.3	Q13585
	GPR50-AS1	ENST00000454196.1	TSL:2	n.461-14G>C		intron	N/A
	GPR50-AS1	ENST00000835194.1		n.440+488G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000367 AC: 4 AN: 1090133 Hom.: 0 Cov.: 28 AF XY: 0.00000562 AC XY: 2 AN XY: 355973

African (AFR) AF: 0.00 AC: 0 AN: 26207

American (AMR) AF: 0.00 AC: 0 AN: 34870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19145

East Asian (EAS) AF: 0.00 AC: 0 AN: 30073

South Asian (SAS) AF: 0.00 AC: 0 AN: 53242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40451

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4078

European-Non Finnish (NFE) AF: 0.00000478 AC: 4 AN: 836256

Other (OTH) AF: 0.00 AC: 0 AN: 45811

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Uncertain	0.53	D
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.016	D
Polyphen		0.20	B
Vest4		0.51
MutPred		0.72		Gain of methylation at N56 (P = 0.0194)
MVP		0.97
MPC		0.22
ClinPred		0.82	D
GERP RS		3.5
PromoterAI		-0.0062	Neutral
Varity_R		0.33
gMVP		0.40
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1246151000; hg19: chrX-150345361;