13-99254940-GC-CA

Variant names:

• chr13-99254940-GC-CA
• NM_001098200.2:c.932_933delGCinsTG
• GPR18 p.Arg311Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001098200.2(GPR18):​c.932_933delGCinsTG​(p.Arg311Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R311C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR18 NM_001098200.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

GPR18 (HGNC:4472): (G protein-coupled receptor 18) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of Rho protein signal transduction and positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to act upstream of or within T cell differentiation; negative regulation of leukocyte chemotaxis; and negative regulation of tumor necrosis factor production. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098200.2. 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
	GPR18	NM_001098200.2	MANE Select	c.932_933delGCinsTG	p.Arg311Leu	missense	N/A	NP_001091670.1	Q14330
	UBAC2	NM_001144072.2	MANE Select	c.389+10316_389+10317delGCinsCA		intron	N/A	NP_001137544.1	Q8NBM4-1
	GPR18	NM_005292.4		c.932_933delGCinsTG	p.Arg311Leu	missense	N/A	NP_005283.1	Q14330

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR18	ENST00000397470.5	TSL:1 MANE Select	c.932_933delGCinsTG	p.Arg311Leu	missense	N/A	ENSP00000380610.2	Q14330
	GPR18	ENST00000340807.3	TSL:1	c.932_933delGCinsTG	p.Arg311Leu	missense	N/A	ENSP00000343428.3	Q14330
	GPR18	ENST00000397473.7	TSL:1	c.932_933delGCinsTG	p.Arg311Leu	missense	N/A	ENSP00000380613.2	Q14330

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-99907194;