11-3217956-C-T

Variant names:

• chr11-3217956-C-T
• rs1208627771
• NM_001164377.1:c.858G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164377.1(MRGPRG):​c.858G>A​(p.Met286Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,339,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09017381).

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.858G>A	p.Met286Ile	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.858G>A	p.Met286Ile	missense	Exon 1 of 1	ENSP00000330612.3	Q86SM5
	MRGPRG-AS1	ENST00000820167.1		n.121+348C>T		intron	N/A
	MRGPRG-AS1	ENST00000820168.1		n.121+132C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000874 AC: 1 AN: 114458 AF XY: 0.0000165

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1339852 Hom.: 0 Cov.: 32 AF XY: 0.00000306 AC XY: 2 AN XY: 653090

African (AFR) AF: 0.00 AC: 0 AN: 30084

American (AMR) AF: 0.00 AC: 0 AN: 30452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22062

East Asian (EAS) AF: 0.00 AC: 0 AN: 34942

South Asian (SAS) AF: 0.0000279 AC: 2 AN: 71800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3872

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045292

Other (OTH) AF: 0.00 AC: 0 AN: 55192

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.026
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.086
Sift	Benign	0.35	T
Sift4G	Benign	0.17	T
Vest4		0.25
MutPred		0.23		Gain of sheet (P = 0.1208)
MVP		0.040
ClinPred		0.091	T
GERP RS		3.7
Varity_R		0.26
gMVP		0.31
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1208627771; hg19: chr11-3239186; COSMIC: COSV108123679; COSMIC: COSV108123679;