Genetic Variant GPR3:p.Ala257Ala (chr1-27394569-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_005281.4(GPR3):c.771C>T(p.Ala257Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,168 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0098 ( 15 hom., cov: 33)

Exomes 𝑓: 0.013 ( 170 hom. )

Consequence

GPR3
NM_005281.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.68

Variant links:

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]

GPR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP7

Synonymous conserved (PhyloP=-4.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0133 (19470/1461852) while in subpopulation NFE AF= 0.0154 (17142/1112000). AF 95% confidence interval is 0.0152. There are 170 homozygotes in gnomad4_exome. There are 9613 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR3	NM_005281.4 link	c.771C>T	p.Ala257Ala	synonymous_variant	Exon 2 of 2	ENST00000374024.4	NP_005272.1	P46089F1DAM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR3	ENST00000374024.4 link	c.771C>T	p.Ala257Ala	synonymous_variant	Exon 2 of 2	1	NM_005281.4	ENSP00000363136.3		P46089

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1491

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00968

AC:

2431

AN:

251024

Hom.:

AF XY:

0.00984

AC XY:

1335

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00683

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00265

Gnomad FIN exome

AF:

0.00698

Gnomad NFE exome

AF:

0.0147

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0133

AC:

19470

AN:

1461852

Hom.:

170

Cov.:

AF XY:

0.0132

AC XY:

9613

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00736

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00291

Gnomad4 FIN exome

AF:

0.00693

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00979

AC:

1491

AN:

152316

Hom.:

Cov.:

AF XY:

0.00943

AC XY:

702

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00960

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.4

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over