rs34585631

Positions:

• chr1-27394034-T-C
• chr1-27394034-T-G

Variant summary

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

The NM_005281.4(GPR3):​c.236T>C​(p.Val79Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96

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

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	Protein	UniProt
GPR3	NM_005281.4	c.236T>C	p.Val79Ala	missense_variant	2/2	ENST00000374024.4	NP_005272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR3	ENST00000374024.4	c.236T>C	p.Val79Ala	missense_variant	2/2	1	NM_005281.4	ENSP00000363136.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74478

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	0.0066	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0077	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.71	P
Vest4		0.51
MutPred		0.62		Loss of helix (P = 0.1299);
MVP		0.75
MPC		0.88
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.73
gMVP		0.73

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: chr1-27720538;