chr6-153008373-G-A

Variant names:

• chr6-153008373-G-A
• rs9397578
• NM_012419.5:c.*3201C>T

Variant summary

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

The NM_012419.5(RGS17):​c.*3201C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 150,900 control chromosomes in the GnomAD database, including 5,957 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 0.28 (5957 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGS17 NM_012419.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.*3201C>T		3_prime_UTR	Exon 5 of 5	NP_036551.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.*3201C>T		3_prime_UTR	Exon 5 of 5	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.*3201C>T		3_prime_UTR	Exon 4 of 4	ENSP00000356194.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42061 AN: 150822 Hom.: 5950 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.259

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.279 AC: 42091 AN: 150900 Hom.: 5957 Cov.: 32 AF XY: 0.279 AC XY: 20566 AN XY: 73588

African (AFR) AF: 0.271 AC: 11133 AN: 41130

American (AMR) AF: 0.276 AC: 4190 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1701 AN: 5144

South Asian (SAS) AF: 0.250 AC: 1196 AN: 4788

European-Finnish (FIN) AF: 0.314 AC: 3183 AN: 10136

Middle Eastern (MID) AF: 0.324 AC: 94 AN: 290

European-Non Finnish (NFE) AF: 0.274 AC: 18544 AN: 67756

Other (OTH) AF: 0.261 AC: 548 AN: 2096

Alfa AF: 0.271 Hom.: 3105

Bravo AF: 0.276

Asia WGS AF: 0.303 AC: 1054 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.32
PhyloP100		-0.033
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: rs9397578; hg19: chr6-153329508;