11-3218066-A-G

Variant names:

• chr11-3218066-A-G
• rs531900362
• NM_001164377.1:c.748T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001164377.1(MRGPRG):​c.748T>C​(p.Tyr250His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,544,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164377.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRG	NM_001164377.1	MANE Select	c.748T>C	p.Tyr250His	missense	Exon 1 of 1	NP_001157849.1	Q86SM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRG	ENST00000332314.3	TSL:6 MANE Select	c.748T>C	p.Tyr250His	missense	Exon 1 of 1	ENSP00000330612.3	Q86SM5
	MRGPRG-AS1	ENST00000820167.1		n.121+458A>G		intron	N/A
	MRGPRG-AS1	ENST00000820168.1		n.121+242A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000727 AC: 11 AN: 151402 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000335 AC: 5 AN: 149172 AF XY: 0.0000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 61 AN: 1393258 Hom.: 0 Cov.: 32 AF XY: 0.0000378 AC XY: 26 AN XY: 686960

African (AFR) AF: 0.0000317 AC: 1 AN: 31538

American (AMR) AF: 0.000225 AC: 8 AN: 35596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25040

East Asian (EAS) AF: 0.00 AC: 0 AN: 35704

South Asian (SAS) AF: 0.00 AC: 0 AN: 78672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.0000474 AC: 51 AN: 1075724

Other (OTH) AF: 0.0000173 AC: 1 AN: 57728

GnomAD4 genome AF: 0.0000726 AC: 11 AN: 151506 Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 6 AN XY: 74064

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.000525 AC: 8 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000301 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000398 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.3
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.45
Sift	Benign	0.094	T
Sift4G	Benign	0.13	T
Vest4		0.43
MutPred		0.84		Gain of disorder (P = 0.0266)
MVP		0.99
ClinPred		0.24	T
GERP RS		2.0
Varity_R		0.098
gMVP		0.71
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs531900362; hg19: chr11-3239296;