NM_005873.3:c.*66T>G

Variant names:

• chr20-64073787-A-C
• rs6011280
• NM_005873.3:c.*66T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005873.3(RGS19):​c.*66T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,422,218 control chromosomes in the GnomAD database, including 83,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (9864 hom., cov: 34)
  • Exomes 𝑓: 0.34 (73859 hom.)
• Consequence: RGS19 NM_005873.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS19	NM_005873.3	MANE Select	c.*66T>G		3_prime_UTR	Exon 6 of 6	NP_005864.1
	RGS19	NM_001039467.2		c.*66T>G		3_prime_UTR	Exon 6 of 6	NP_001034556.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS19	ENST00000395042.2	TSL:1 MANE Select	c.*66T>G		3_prime_UTR	Exon 6 of 6	ENSP00000378483.1
	RGS19	ENST00000332298.9	TSL:1	c.*66T>G		3_prime_UTR	Exon 6 of 6	ENSP00000333194.5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53934 AN: 152022 Hom.: 9830 Cov.: 34

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.337 AC: 428095 AN: 1270078 Hom.: 73859 Cov.: 19 AF XY: 0.343 AC XY: 215881 AN XY: 629414

African (AFR) AF: 0.422 AC: 12318 AN: 29206

American (AMR) AF: 0.296 AC: 10584 AN: 35806

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 8044 AN: 20904

East Asian (EAS) AF: 0.242 AC: 9290 AN: 38356

South Asian (SAS) AF: 0.487 AC: 35652 AN: 73220

European-Finnish (FIN) AF: 0.304 AC: 11835 AN: 38964

Middle Eastern (MID) AF: 0.417 AC: 1606 AN: 3848

European-Non Finnish (NFE) AF: 0.328 AC: 320190 AN: 976364

Other (OTH) AF: 0.348 AC: 18576 AN: 53410

GnomAD4 genome AF: 0.355 AC: 54030 AN: 152140 Hom.: 9864 Cov.: 34 AF XY: 0.355 AC XY: 26434 AN XY: 74384

African (AFR) AF: 0.416 AC: 17285 AN: 41508

American (AMR) AF: 0.327 AC: 5006 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1296 AN: 5180

South Asian (SAS) AF: 0.487 AC: 2348 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3219 AN: 10596

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22397 AN: 67960

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.345 Hom.: 18645

Bravo AF: 0.359

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs6011280; hg19: chr20-62705140; COSMIC: COSV58659790; COSMIC: COSV58659790;