8-141357215-C-A

Variant names:

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

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>T​(p.Val237Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,415,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GPR20 NM_005293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 2 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=0.091220975).

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000579 AC: 1 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: 0.0000136

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1415282 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 701114

African (AFR) AF: 0.0000307 AC: 1 AN: 32526

American (AMR) AF: 0.00 AC: 0 AN: 37994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 37318

South Asian (SAS) AF: 0.00 AC: 0 AN: 82350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091862

Other (OTH) AF: 0.00 AC: 0 AN: 58874

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000858 AC: 1

ClinVar

Not reported in ClinVar

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	8.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.091	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		0.12	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;