6-153043965-A-C

Position:

• chr6-153043965-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012419.5(RGS17):​c.54T>G​(p.Ala18=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS17	NM_012419.5	c.54T>G	p.Ala18=	synonymous_variant	2/5	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.99T>G	p.Ala33=	synonymous_variant	2/5		XP_047274590.1
RGS17	XM_047418635.1	c.87T>G	p.Ala29=	synonymous_variant	2/5		XP_047274591.1
RGS17	XM_047418636.1	c.54T>G	p.Ala18=	synonymous_variant	2/5		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.54T>G	p.Ala18=	synonymous_variant	2/5	1	NM_012419.5	ENSP00000206262	P1
RGS17	ENST00000367225.6	c.54T>G	p.Ala18=	synonymous_variant	1/4	1		ENSP00000356194	P1

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

GnomAD3 exomes AF: 0.384 AC: 95916 AN: 249666 Hom.: 20079 AF XY: 0.380 AC XY: 51315 AN XY: 135030

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 SAS exome AF: 0.486

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

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.349

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

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.375

Alfa AF: 0.297 Hom.: 2981

Bravo AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295230; hg19: chr6-153365100; COSMIC: COSV52806105;