Genetic Variant MRGPRG:p.Gly202Ser (chr11-3218210-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001164377.1(MRGPRG):c.604G>A(p.Gly202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,381,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000058 ( 0 hom. )

Consequence

MRGPRG
NM_001164377.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283

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:

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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=0.14561605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRG	NM_001164377.1 link	c.604G>A	p.Gly202Ser	missense_variant	Exon 1 of 1	ENST00000332314.3	NP_001157849.1	Q86SM5
MRGPRG-AS1	NR_027138.1 link	n.-122C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRGPRG	ENST00000332314.3 link	c.604G>A	p.Gly202Ser	missense_variant	Exon 1 of 1	6	NM_001164377.1	ENSP00000330612.3	Q86SM5
MRGPRG-AS1	ENST00000420873.2 link	n.-178C>T		upstream_gene_variant		2
MRGPRG-AS1	ENST00000434798.1 link	n.-122C>T		upstream_gene_variant		2
MRGPRG-AS1	ENST00000531711.1 link	n.-157C>T		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000579

AC:

AN:

1381728

Hom.:

Cov.:

AF XY:

0.00000442

AC XY:

AN XY:

679428

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.604G>A (p.G202S) 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 604, causing the glycine (G) at amino acid position 202 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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.6

DANN

Benign

0.69

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.47

M_CAP

Benign

0.0028

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.28

PROVEAN

Benign

0.030

REVEL

Benign

0.030

Sift

Benign

0.24

Sift4G

Benign

0.10

Vest4

0.16

MutPred

0.59

Loss of sheet (P = 0.1158);

MVP

0.57

ClinPred

0.054

GERP RS

-2.2

Varity_R

0.043

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over