chr6-153043965-A-C

Variant names:

• chr6-153043965-A-C
• rs2295230
• NM_012419.5:c.54T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012419.5(RGS17):​c.54T>G​(p.Ala18Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,610,784 control chromosomes in the GnomAD database, including 95,162 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 0.40 (13221 hom., cov: 32)
  • Exomes 𝑓: 0.32 (81941 hom.)
• Consequence: RGS17 NM_012419.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 15 publications found

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012419.5. 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
	RGS17	NM_012419.5	MANE Select	c.54T>G	p.Ala18Ala	synonymous	Exon 2 of 5	NP_036551.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.54T>G	p.Ala18Ala	synonymous	Exon 2 of 5	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.54T>G	p.Ala18Ala	synonymous	Exon 1 of 4	ENSP00000356194.1
	RGS17	ENST00000914255.1		c.54T>G	p.Ala18Ala	synonymous	Exon 2 of 4	ENSP00000584314.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60820 AN: 151814 Hom.: 13197 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.384 AC: 95916 AN: 249666 AF XY: 0.380

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.323 AC: 471383 AN: 1458850 Hom.: 81941 Cov.: 32 AF XY: 0.327 AC XY: 237470 AN XY: 725854

African (AFR) AF: 0.572 AC: 19042 AN: 33272

American (AMR) AF: 0.430 AC: 19108 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8176 AN: 26088

East Asian (EAS) AF: 0.594 AC: 23485 AN: 39510

South Asian (SAS) AF: 0.483 AC: 41587 AN: 86026

European-Finnish (FIN) AF: 0.338 AC: 18058 AN: 53394

Middle Eastern (MID) AF: 0.423 AC: 2432 AN: 5756

European-Non Finnish (NFE) AF: 0.287 AC: 318454 AN: 1110032

Other (OTH) AF: 0.349 AC: 21041 AN: 60286

GnomAD4 genome AF: 0.401 AC: 60892 AN: 151934 Hom.: 13221 Cov.: 32 AF XY: 0.405 AC XY: 30059 AN XY: 74246

African (AFR) AF: 0.557 AC: 23069 AN: 41396

American (AMR) AF: 0.390 AC: 5958 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3193 AN: 5146

South Asian (SAS) AF: 0.503 AC: 2418 AN: 4810

European-Finnish (FIN) AF: 0.349 AC: 3692 AN: 10568

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20328 AN: 67974

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.297 Hom.: 2981

Bravo AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.29
PhyloP100		-1.2
PromoterAI		-0.038	Neutral
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: rs2295230; hg19: chr6-153365100; COSMIC: COSV52806105;