Variant 11-3218485-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001164377.1(MRGPRG):c.329C>G(p.Pro110Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,544,400 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 9 hom. )

Consequence

MRGPRG
NM_001164377.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRG	NM_001164377.1 linkuse as main transcript	c.329C>G	p.Pro110Arg	missense_variant	1/1	ENST00000332314.3	NP_001157849.1
MRGPRG-AS1	NR_027138.1 linkuse as main transcript	n.154G>C		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.329C>G	p.Pro110Arg	missense_variant	1/1		NM_001164377.1	ENSP00000330612	P1
MRGPRG-AS1	ENST00000434798.1 linkuse as main transcript	n.154G>C		non_coding_transcript_exon_variant	1/2	2
MRGPRG-AS1	ENST00000420873.2 linkuse as main transcript	n.98G>C		non_coding_transcript_exon_variant	1/3	2
MRGPRG-AS1	ENST00000531711.1 linkuse as main transcript	n.119G>C		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000190

AC:

AN:

147422

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

78896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000887

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000118

AC:

164

AN:

1393040

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

107

AN XY:

686986

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000787

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000799

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151360

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000418

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 18, 2022

The c.329C>G (p.P110R) alteration is located in exon 1 (coding exon 1) of the MRGPRG gene. This alteration results from a C to G substitution at nucleotide position 329, causing the proline (P) at amino acid position 110 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.50

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.6

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-8.3

REVEL

Uncertain

0.39

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Vest4

0.47

MVP

0.70

ClinPred

0.44

GERP RS

2.8

Varity_R

0.31

gMVP

0.52

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