3-71754317-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018971.3(GPR27):c.268C>G(p.Pro90Ala) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPR27 NM_018971.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15399203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR27	NM_018971.3	c.268C>G	p.Pro90Ala	missense_variant	1/1	ENST00000304411.3
EIF4E3	NM_001134649.3	c.-393G>C		5_prime_UTR_variant	1/8
EIF4E3	XM_047448063.1	c.-515G>C		5_prime_UTR_variant	1/9
EIF4E3	NM_173359.5	c.-291+327G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR27	ENST00000304411.3	c.268C>G	p.Pro90Ala	missense_variant	1/1		NM_018971.3	P1
EIF4E3	ENST00000421769.6	c.-291+327G>C		intron_variant		1
EIF4E3	ENST00000448225.5	c.-393G>C		5_prime_UTR_variant	1/8	5
EIF4E3	ENST00000496214.6	c.-393G>C		5_prime_UTR_variant	1/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1018880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 483898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

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

Jul 25, 2023

The c.268C>G (p.P90A) 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 268, causing the proline (P) at amino acid position 90 to be replaced by an alanine (A). 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	0.056
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.050	N
REVEL	Benign	0.076
Sift	Benign	0.060	T
Sift4G	Benign	0.58	T
Polyphen		0.059	B
Vest4		0.22
MutPred		0.60		Loss of glycosylation at P90 (P = 0.0095);
MVP		0.082
ClinPred		0.32	T
GERP RS		3.0
Varity_R		0.058
gMVP		0.13

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: chr3-71803468;