rs1451841663

Variant names:

• chr20-64074506-C-A
• rs1451841663
• NM_005873.3:c.188G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-64074506-C-A
• chr20-64074506-C-G
• chr20-64074506-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005873.3(RGS19):​c.188G>T​(p.Arg63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000507 in 1,578,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R63Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: RGS19 NM_005873.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 2 publications found

Genes affected

RGS19 (HGNC:13735): (regulator of G protein signaling 19) G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2069608).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005873.3. 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
	RGS19	NM_005873.3	MANE Select	c.188G>T	p.Arg63Leu	missense	Exon 4 of 6	NP_005864.1	P49795
	RGS19	NM_001039467.2		c.188G>T	p.Arg63Leu	missense	Exon 4 of 6	NP_001034556.1	P49795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS19	ENST00000395042.2	TSL:1 MANE Select	c.188G>T	p.Arg63Leu	missense	Exon 4 of 6	ENSP00000378483.1	P49795
	RGS19	ENST00000332298.9	TSL:1	c.188G>T	p.Arg63Leu	missense	Exon 4 of 6	ENSP00000333194.5	P49795
	RGS19	ENST00000910389.1		c.230G>T	p.Arg77Leu	missense	Exon 4 of 6	ENSP00000580448.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000107 AC: 2 AN: 186768 AF XY: 0.00000988

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: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1426486 Hom.: 0 Cov.: 34 AF XY: 0.00000425 AC XY: 3 AN XY: 706574

African (AFR) AF: 0.00 AC: 0 AN: 32758

American (AMR) AF: 0.00 AC: 0 AN: 39574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 37692

South Asian (SAS) AF: 0.0000610 AC: 5 AN: 82006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095304

Other (OTH) AF: 0.0000170 AC: 1 AN: 58978

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152318 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.027
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.026	D
Sift4G	Benign	0.64	T
Polyphen		0.29	B
Vest4		0.50
MutPred		0.33		Loss of MoRF binding (P = 0.0391)
MVP		0.47
MPC		0.68
ClinPred		0.28	T
GERP RS		3.1
Varity_R		0.12
gMVP		0.70
Mutation Taster		=88/12	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: rs1451841663; hg19: chr20-62705859;