rs932805803

Variant names:

• chr11-3218440-A-C
• rs932805803
• NM_001164377.1:c.374T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-3218440-A-C
• chr11-3218440-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001164377.1(MRGPRG):​c.374T>G​(p.Leu125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L125P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

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.374T>G	p.Leu125Arg	missense	Exon 1 of 1	NP_001157849.1	Q86SM5
	MRGPRG-AS1	NR_027138.1		n.109A>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRG	ENST00000332314.3	TSL:6 MANE Select	c.374T>G	p.Leu125Arg	missense	Exon 1 of 1	ENSP00000330612.3	Q86SM5
	MRGPRG-AS1	ENST00000420873.2	TSL:2	n.53A>C		non_coding_transcript_exon	Exon 1 of 3
	MRGPRG-AS1	ENST00000434798.1	TSL:2	n.109A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 684246

African (AFR) AF: 0.00 AC: 0 AN: 31474

American (AMR) AF: 0.00 AC: 0 AN: 35530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24888

East Asian (EAS) AF: 0.00 AC: 0 AN: 35688

South Asian (SAS) AF: 0.00 AC: 0 AN: 78480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4938

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075056

Other (OTH) AF: 0.00 AC: 0 AN: 57580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0038	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.53
MutPred		0.84		Gain of methylation at L125 (P = 0.0405)
MVP		0.35
ClinPred		0.85	D
GERP RS		1.4
PromoterAI		-0.0039	Neutral
Varity_R		0.32
gMVP		0.55
Mutation Taster		=99/1	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: rs932805803; hg19: chr11-3239670;