chr3-71754544-C-G

Position:

chr3-71754544-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018971.3(GPR27):c.495C>G(p.Asp165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,349,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

GPR27
NM_018971.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

GPR27 (HGNC:4482): (G protein-coupled receptor 27) GPR27 is a member of the G protein-coupled receptors (GPCRs), a large family of receptors that have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli such as neurotransmitters, hormones, or light induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins.[supplied by OMIM, May 2010]

GPR27 links:

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

EIF4E3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0071564913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPR27	NM_018971.3 linkuse as main transcript	c.495C>G	p.Asp165Glu	missense_variant	1/1	ENST00000304411.3	NP_061844.1
EIF4E3	NM_173359.5 linkuse as main transcript	c.-291+100G>C		intron_variant			NP_775495.1
EIF4E3	NM_001134649.3 linkuse as main transcript			upstream_gene_variant			NP_001128121.1
EIF4E3	XM_047448063.1 linkuse as main transcript			upstream_gene_variant			XP_047304019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR27	ENST00000304411.3 linkuse as main transcript	c.495C>G	p.Asp165Glu	missense_variant	1/1		NM_018971.3	ENSP00000303149	P1
EIF4E3	ENST00000421769.6 linkuse as main transcript	c.-291+100G>C		intron_variant		1		ENSP00000411762		Q8N5X7-2

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

155

AN:

150090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000331

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

32842

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

19530

show subpopulations

Gnomad AFR exome

AF:

0.00573

Gnomad AMR exome

AF:

0.000489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000817

AC:

AN:

1199386

Hom.:

Cov.:

AF XY:

0.0000852

AC XY:

AN XY:

586994

show subpopulations

Gnomad4 AFR exome

AF:

0.00380

Gnomad4 AMR exome

AF:

0.000132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.00103

AC:

154

AN:

150198

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

73360

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.000331

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.00125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.495C>G (p.D165E) alteration is located in exon 1 (coding exon 1) of the GPR27 gene. This alteration results from a C to G substitution at nucleotide position 495, causing the aspartic acid (D) at amino acid position 165 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.20

M_CAP

Benign

0.029

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.28

REVEL

Benign

0.067

Sift

Benign

0.23

Sift4G

Benign

0.35

Polyphen

0.027

Vest4

0.061

MutPred

0.57

Loss of helix (P = 0.1706);

MVP

0.043

ClinPred

0.013

GERP RS

1.8

Varity_R

0.12

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over