1-27394504-G-C

Variant names:

• chr1-27394504-G-C
• rs372362016
• NM_005281.4:c.706G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005281.4(GPR3):​c.706G>C​(p.Ala236Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. A236S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 0 publications found

Genes affected

GPR3 (HGNC:4484): (G protein-coupled receptor 3) This gene is a member of the G protein-coupled receptor family and is found in the cell membrane. G protein-coupled receptors, characterized by a seven transmembrane domain motif, are involved in translating outside signals into G protein mediated intracellular effects. The encoded protein activates adenylate cyclase and modulates amyloid-beta production in a mouse model, suggesting that it may play a role in Alzheimer's disease. [provided by RefSeq, Oct 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07786879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR3	NM_005281.4	c.706G>C	p.Ala236Pro	missense_variant	Exon 2 of 2	ENST00000374024.4	NP_005272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR3	ENST00000374024.4	c.706G>C	p.Ala236Pro	missense_variant	Exon 2 of 2	1	NM_005281.4	ENSP00000363136.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000660 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.31	N
PhyloP100		0.96
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.067
Sift	Benign	0.23	T
Sift4G	Benign	0.26	T
Polyphen		0.0070	B
Vest4		0.069
MutPred		0.63		Gain of catalytic residue at P235 (P = 0.0146);
MVP		0.45
MPC		0.53
ClinPred		0.083	T
GERP RS		3.8
Varity_R		0.072
gMVP		0.79
Mutation Taster		=89/11	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: rs372362016; hg19: chr1-27721008;