11-3218063-A-G

Variant names:

• chr11-3218063-A-G
• NM_001164377.1:c.751T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164377.1(MRGPRG):​c.751T>C​(p.Ser251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,393,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000022 (0 hom.)
• Consequence: MRGPRG NM_001164377.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1704537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRG	NM_001164377.1	c.751T>C	p.Ser251Pro	missense_variant	Exon 1 of 1	ENST00000332314.3	NP_001157849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGPRG	ENST00000332314.3	c.751T>C	p.Ser251Pro	missense_variant	Exon 1 of 1	6	NM_001164377.1	ENSP00000330612.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1393140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 686880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.751T>C (p.S251P) alteration is located in exon 1 (coding exon 1) of the MRGPRG gene. This alteration results from a T to C substitution at nucleotide position 751, causing the serine (S) at amino acid position 251 to be replaced by a proline (P). 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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.3
DANN	Benign	0.91
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.024
Sift	Benign	0.034	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.38
MutPred		0.51		Loss of glycosylation at S251 (P = 0.051);
MVP		0.31
ClinPred		0.074	T
GERP RS		1.8
Varity_R		0.12
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3239293;