NM_004224.3:c.340G>T

Variant names:

• chrX-151179923-G-T
• rs772438504
• NM_004224.3:c.340G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004224.3(GPR50):​c.340G>T​(p.Gly114Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 110,872 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. G114S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 22)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.340G>T	p.Gly114Cys	missense	Exon 2 of 2	NP_004215.2	Q13585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	ENST00000218316.4	TSL:1 MANE Select	c.340G>T	p.Gly114Cys	missense	Exon 2 of 2	ENSP00000218316.3	Q13585

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 110872 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 110872 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33124

African (AFR) AF: 0.0000658 AC: 2 AN: 30373

American (AMR) AF: 0.00 AC: 0 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5957

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52961

Other (OTH) AF: 0.00 AC: 0 AN: 1481

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.58	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Uncertain	0.37
Sift	Benign	0.071	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.44	B
Vest4		0.52
MVP		0.98
MPC		0.44
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.72
gMVP		0.85
Mutation Taster		=75/25	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: rs772438504; hg19: chrX-150348395;