rs1368659617

Variant names:

• chr1-27393923-C-A
• rs1368659617
• NM_005281.4:c.125C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-27393923-C-A
• chr1-27393923-C-G
• chr1-27393923-C-T

Variant summary

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

The NM_005281.4(GPR3):​c.125C>A​(p.Ala42Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A42V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 rank	MANE	Protein	UniProt
GPR3	NM_005281.4	c.125C>A	p.Ala42Asp	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.125C>A	p.Ala42Asp	missense_variant	Exon 2 of 2	1	NM_005281.4	ENSP00000363136.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Benign	0.0090
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.024	D
Polyphen		0.63	P
Vest4		0.82
MutPred		0.47		Loss of catalytic residue at A42 (P = 0.0166);
MVP		0.75
MPC		0.71
ClinPred		0.71	D
GERP RS		4.3
Varity_R		0.35
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs1368659617; hg19: chr1-27720427;