11-3218456-G-A

Variant names:

• chr11-3218456-G-A
• rs1426038419
• NM_001164377.1:c.358C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164377.1(MRGPRG):​c.358C>T​(p.His120Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,390,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.0000036 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4221689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRG	NM_001164377.1	c.358C>T	p.His120Tyr	missense_variant	Exon 1 of 1	ENST00000332314.3	NP_001157849.1
MRGPRG-AS1	NR_027138.1	n.125G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGPRG	ENST00000332314.3	c.358C>T	p.His120Tyr	missense_variant	Exon 1 of 1	6	NM_001164377.1	ENSP00000330612.3
MRGPRG-AS1	ENST00000420873.2	n.69G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
MRGPRG-AS1	ENST00000434798.1	n.125G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
MRGPRG-AS1	ENST00000531711.1	n.90G>A		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000702 AC: 1 AN: 142396 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76802

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000360 AC: 5 AN: 1390572 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 2 AN XY: 685828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000281

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: 0.0000173

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358C>T (p.H120Y) alteration is located in exon 1 (coding exon 1) of the MRGPRG gene. This alteration results from a C to T substitution at nucleotide position 358, causing the histidine (H) at amino acid position 120 to be replaced by a tyrosine (Y). 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	0.091
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.9
DANN	Benign	0.92
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.077
Sift	Benign	0.16	T
Sift4G	Uncertain	0.049	D
Vest4		0.12
MutPred		0.83		Gain of catalytic residue at H120 (P = 0.0589);
MVP		0.53
ClinPred		0.16	T
GERP RS		-0.28
Varity_R		0.084
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1426038419; hg19: chr11-3239686;