1-27393874-C-T

Position:

• chr1-27393874-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005281.4(GPR3):​c.76C>T​(p.Pro26Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044866055).
• BP6: Variant 1-27393874-C-T is Benign according to our data. Variant chr1-27393874-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3522008.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR3	NM_005281.4	c.76C>T	p.Pro26Ser	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.76C>T	p.Pro26Ser	missense_variant	2/2	1	NM_005281.4	ENSP00000363136.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.077
Sift	Benign	0.68	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.14		Loss of sheet (P = 0.003);
MVP		0.35
MPC		0.40
ClinPred		0.033	T
GERP RS		1.8
Varity_R		0.030
gMVP		0.17

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: chr1-27720378;