3-71754791-C-G

Position:

• chr3-71754791-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018971.3(GPR27):​c.742C>G​(p.Arg248Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR27 NM_018971.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3594616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR27	NM_018971.3	c.742C>G	p.Arg248Gly	missense_variant	1/1	ENST00000304411.3	NP_061844.1
EIF4E3	NM_173359.5	c.-438G>C		upstream_gene_variant			NP_775495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR27	ENST00000304411.3	c.742C>G	p.Arg248Gly	missense_variant	1/1	6	NM_018971.3	ENSP00000303149.2
EIF4E3	ENST00000421769.6	c.-438G>C		upstream_gene_variant		1		ENSP00000411762.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.742C>G (p.R248G) 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 742, causing the arginine (R) at amino acid position 248 to be replaced by a glycine (G). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.0037
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.62		Loss of solvent accessibility (P = 0.001);
MVP		0.068
ClinPred		0.97	D
GERP RS		0.67
Varity_R		0.50
gMVP		0.75

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: chr3-71803942;