Variant 11-3218620-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164377.1(MRGPRG):c.194T>C(p.Val65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,902 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000014 ( 1 hom. )

Consequence

MRGPRG
NM_001164377.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

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:):

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=0.079926044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRG	NM_001164377.1 linkuse as main transcript	c.194T>C	p.Val65Ala	missense_variant	1/1	ENST00000332314.3	NP_001157849.1	Q86SM5
MRGPRG-AS1	NR_027138.1 linkuse as main transcript	n.228+61A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MRGPRG	ENST00000332314.3 linkuse as main transcript	c.194T>C	p.Val65Ala	missense_variant	1/1	6	NM_001164377.1	ENSP00000330612.3	Q86SM5
MRGPRG-AS1	ENST00000420873.2 linkuse as main transcript	n.172+61A>G		intron_variant		2
MRGPRG-AS1	ENST00000434798.1 linkuse as main transcript	n.228+61A>G		intron_variant		2
MRGPRG-AS1	ENST00000531711.1 linkuse as main transcript	n.193+61A>G		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394902

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687882

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:

0.00000186

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.194T>C (p.V65A) alteration is located in exon 1 (coding exon 1) of the MRGPRG gene. This alteration results from a T to C substitution at nucleotide position 194, causing the valine (V) at amino acid position 65 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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.0

DANN

Benign

0.60

DEOGEN2

Benign

0.010

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.25

M_CAP

Benign

0.0026

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.056

Sift

Benign

0.44

Sift4G

Uncertain

0.051

Vest4

0.037

MutPred

0.55

Loss of stability (P = 0.0111);

MVP

0.17

ClinPred

0.050

GERP RS

1.0

Varity_R

0.076

gMVP

0.37

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.

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