chr11-3218216-C-A

Variant names:

• chr11-3218216-C-A
• rs536671714
• NM_001164377.1:c.598G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164377.1(MRGPRG):​c.598G>T​(p.Val200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000654 in 1,529,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V200L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33222502).

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.598G>T	p.Val200Phe	missense	Exon 1 of 1	NP_001157849.1	Q86SM5
	MRGPRG-AS1	NR_027138.1		n.-116C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRG	ENST00000332314.3	TSL:6 MANE Select	c.598G>T	p.Val200Phe	missense	Exon 1 of 1	ENSP00000330612.3	Q86SM5
	MRGPRG-AS1	ENST00000820167.1		n.121+608C>A		intron	N/A
	MRGPRG-AS1	ENST00000820168.1		n.121+392C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151412 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000146 AC: 2 AN: 136622 AF XY: 0.0000138

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: 0.0000403

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000436 AC: 6 AN: 1377620 Hom.: 0 Cov.: 32 AF XY: 0.00000443 AC XY: 3 AN XY: 676794

African (AFR) AF: 0.00 AC: 0 AN: 31182

American (AMR) AF: 0.00 AC: 0 AN: 34568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24104

East Asian (EAS) AF: 0.00 AC: 0 AN: 35422

South Asian (SAS) AF: 0.00 AC: 0 AN: 76722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00000563 AC: 6 AN: 1066074

Other (OTH) AF: 0.00 AC: 0 AN: 57002

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151412 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41286

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000591 AC: 4 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00585934), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000514 Hom.: 0

Bravo AF: 0.0000302

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	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.061
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0070	D
Vest4		0.33
MutPred		0.68		Gain of solvent accessibility (P = 0.039)
MVP		0.22
ClinPred		0.20	T
GERP RS		-3.8
Varity_R		0.085
gMVP		0.52
Mutation Taster		=95/5	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: rs536671714; hg19: chr11-3239446;