3-71754299-G-T

Position:

chr3-71754299-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018971.3(GPR27):c.250G>T(p.Ala84Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000765 in 1,150,468 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

GPR27
NM_018971.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

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 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=0.10456988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPR27	NM_018971.3 linkuse as main transcript	c.250G>T	p.Ala84Ser	missense_variant	1/1	ENST00000304411.3	NP_061844.1
EIF4E3	NM_001134649.3 linkuse as main transcript	c.-375C>A		5_prime_UTR_variant	1/8		NP_001128121.1
EIF4E3	XM_047448063.1 linkuse as main transcript	c.-497C>A		5_prime_UTR_variant	1/9		XP_047304019.1
EIF4E3	NM_173359.5 linkuse as main transcript	c.-291+345C>A		intron_variant			NP_775495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR27	ENST00000304411.3 linkuse as main transcript	c.250G>T	p.Ala84Ser	missense_variant	1/1		NM_018971.3	ENSP00000303149	P1
EIF4E3	ENST00000421769.6 linkuse as main transcript	c.-291+345C>A		intron_variant		1		ENSP00000411762		Q8N5X7-2
EIF4E3	ENST00000448225.5 linkuse as main transcript	c.-375C>A		5_prime_UTR_variant	1/8	5		ENSP00000410350		Q8N5X7-2
EIF4E3	ENST00000496214.6 linkuse as main transcript	c.-375C>A		5_prime_UTR_variant	1/6	5		ENSP00000417889

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

148172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000671

Gnomad ASJ

AF:

0.00383

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.000490

GnomAD4 exome

AF:

0.0000718

AC:

AN:

1002296

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

474332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.00412

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000218

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000108

AC:

AN:

148172

Hom.:

Cov.:

AF XY:

0.0000970

AC XY:

AN XY:

72134

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000671

Gnomad4 ASJ

AF:

0.00383

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.000490

Bravo

AF:

0.000128

ExAC

AF:

0.0000920

AC:

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

Nov 21, 2022

The c.250G>T (p.A84S) alteration is located in exon 1 (coding exon 1) of the GPR27 gene. This alteration results from a G to T substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.51

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.32

REVEL

Benign

0.13

Sift

Benign

0.48

Sift4G

Benign

0.49

Polyphen

0.11

Vest4

0.28

MutPred

0.47

Gain of glycosylation at A84 (P = 0.0012);

MVP

0.29

ClinPred

0.67

GERP RS

3.0

Varity_R

0.11

gMVP

0.12

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