X-151179882-A-C

Position:

• chrX-151179882-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004224.3(GPR50):​c.299A>C​(p.Gln100Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR50	NM_004224.3	c.299A>C	p.Gln100Pro	missense_variant	2/2	ENST00000218316.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4	c.299A>C	p.Gln100Pro	missense_variant	2/2	1	NM_004224.3	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

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 31, 2024

The c.299A>C (p.Q100P) alteration is located in exon 2 (coding exon 2) of the GPR50 gene. This alteration results from a A to C substitution at nucleotide position 299, causing the glutamine (Q) at amino acid position 100 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	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.22
Sift	Benign	0.12	T
Sift4G	Uncertain	0.042	D
Polyphen		0.078	B
Vest4		0.54
MutPred		0.81		Gain of helix (P = 0.2059);
MVP		0.81
MPC		0.29
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.76
gMVP		0.92

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: chrX-150348354;