8-141357215-C-G

Variant names:

• chr8-141357215-C-G
• rs574585646
• NM_005293.3:c.709G>C

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.709G>C​(p.Val237Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: GPR20 NM_005293.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0990
• 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=0.08817217).

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.709G>C	p.Val237Leu	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.709G>C	p.Val237Leu	missense	Exon 2 of 2	ENSP00000366970.3	Q99678
	GPR20	ENST00000887272.1		c.709G>C	p.Val237Leu	missense	Exon 2 of 2	ENSP00000557331.1
	GPR20	ENST00000887273.1		c.709G>C	p.Val237Leu	missense	Exon 2 of 2	ENSP00000557332.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 172652 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.0
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.099
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.056
Sift	Benign	0.37	T
Sift4G	Benign	0.48	T
Polyphen		0.024	B
Vest4		0.099
MutPred		0.42		Loss of helix (P = 0.0558)
MVP		0.42
MPC		0.29
ClinPred		0.26	T
GERP RS		1.4
Varity_R		0.083
gMVP		0.26
Mutation Taster		=95/5	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: rs574585646; hg19: chr8-142367315;