Variant 11-3218464-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164377.1(MRGPRG):c.350G>A(p.Arg117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,391,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

MRGPRG
NM_001164377.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.738

Variant links:

Genes affected

MRGPRG (HGNC:24829): (MAS related GPR family member G) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRG links:

MRGPRG-AS1 (HGNC:26691): (MRGPRG antisense RNA 1)

MRGPRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRG	NM_001164377.1 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	1/1	ENST00000332314.3	NP_001157849.1
MRGPRG-AS1	NR_027138.1 linkuse as main transcript	n.133C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MRGPRG	ENST00000332314.3 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	1/1		NM_001164377.1	ENSP00000330612	P1
MRGPRG-AS1	ENST00000434798.1 linkuse as main transcript	n.133C>T		non_coding_transcript_exon_variant	1/2	2
MRGPRG-AS1	ENST00000420873.2 linkuse as main transcript	n.77C>T		non_coding_transcript_exon_variant	1/3	2
MRGPRG-AS1	ENST00000531711.1 linkuse as main transcript	n.98C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

143442

Hom.:

AF XY:

0.0000129

AC XY:

AN XY:

77242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000943

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000431

AC:

AN:

1391274

Hom.:

Cov.:

AF XY:

0.00000729

AC XY:

AN XY:

686150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000508

Gnomad4 FIN exome

AF:

0.0000218

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000434

AC:

Asia WGS

AF:

0.000580

AC:

AN:

3464

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

Mar 15, 2023

The c.350G>A (p.R117Q) alteration is located in exon 1 (coding exon 1) of the MRGPRG gene. This alteration results from a G to A substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.63

M_CAP

Benign

0.0097

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.14

Sift

Uncertain

0.014

Sift4G

Uncertain

0.055

Vest4

0.11

MutPred

0.92

Loss of solvent accessibility (P = 0.1077);

MVP

0.60

ClinPred

0.42

GERP RS

3.0

Varity_R

0.16

gMVP

0.36

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