chr6-153008373-G-A

Position:

• chr6-153008373-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS17	NM_012419.5	c.*3201C>T		3_prime_UTR_variant	5/5	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.*3201C>T		3_prime_UTR_variant	5/5		XP_047274590.1
RGS17	XM_047418635.1	c.*3201C>T		3_prime_UTR_variant	5/5		XP_047274591.1
RGS17	XM_047418636.1	c.*3201C>T		3_prime_UTR_variant	5/5		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.*3201C>T		3_prime_UTR_variant	5/5	1	NM_012419.5	ENSP00000206262	P1
RGS17	ENST00000367225.6	c.*3201C>T		3_prime_UTR_variant	4/4	1		ENSP00000356194	P1

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.261

Alfa AF: 0.271 Hom.: 2010

Bravo AF: 0.276

Asia WGS AF: 0.303 AC: 1054 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.32

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: rs9397578; hg19: chr6-153329508;