GPR20 p.Val264Leu

Variant names:

• chr8-141357134-C-A
• NM_005293.3:c.790G>T
• GPR20 p.Val264Leu

Your query was ambiguous. Multiple possible variants found:

• chr8-141357134-C-A
• chr8-141357134-C-G
• chr8-141357132-CAC-TAA
• chr8-141357132-CAC-AAG
• chr8-141357132-CAC-GAG
• chr8-141357132-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005293.3(GPR20):​c.790G>T​(p.Val264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. V264M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GPR20 NM_005293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

GPR20 (HGNC:4475): (G protein-coupled receptor 20) Enables 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. Located in cytosol and plasma membrane. Is integral component of plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14867532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005293.3. 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
	GPR20	NM_005293.3	MANE Select	c.790G>T	p.Val264Leu	missense	Exon 2 of 2	NP_005284.2	Q99678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR20	ENST00000377741.4	TSL:3 MANE Select	c.790G>T	p.Val264Leu	missense	Exon 2 of 2	ENSP00000366970.3	Q99678
	GPR20	ENST00000887272.1		c.790G>T	p.Val264Leu	missense	Exon 2 of 2	ENSP00000557331.1
	GPR20	ENST00000887273.1		c.790G>T	p.Val264Leu	missense	Exon 2 of 2	ENSP00000557332.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		1.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.052
Sift	Benign	0.21	T
Sift4G	Benign	0.68	T
Varity_R		0.12
gMVP		0.46
Mutation Taster		=93/7	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

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

Other links and lift over

hg19: chr8-142367234;