rs11199005

chr10-119536517-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392865.5(RGS10):c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 1,607,164 control chromosomes in the GnomAD database, including 5,368 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 0.062 (395 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4973 hom.)
• Consequence: RGS10 ENST00000392865.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

RGS10 (HGNC:9992): (regulator of G protein signaling 10) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 10 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. This protein associates specifically with the activated forms of the two related G-protein subunits, G-alphai3 and G-alphaz but fails to interact with the structurally and functionally distinct G-alpha subunits. Regulator of G protein signaling 10 protein is localized in the nucleus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS10	NM_001005339.2	c.49+6073C>T		intron_variant		ENST00000369103.3
RGS10	NM_002925.4	c.-47C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS10	ENST00000392865.5	c.-47C>T		5_prime_UTR_variant	1/5	1
RGS10	ENST00000369103.3	c.49+6073C>T		intron_variant		1	NM_001005339.2	P1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9393 AN: 152124 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.0612 AC: 14532 AN: 237564 Hom.: 557 AF XY: 0.0620 AC XY: 7988 AN XY: 128884

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.0572

Gnomad ASJ exome AF: 0.0717

Gnomad EAS exome AF: 0.000403

Gnomad SAS exome AF: 0.0270

Gnomad FIN exome AF: 0.0333

Gnomad NFE exome AF: 0.0889

Gnomad OTH exome AF: 0.0816

GnomAD4 exome AF: 0.0783 AC: 113978 AN: 1454922 Hom.: 4973 Cov.: 30 AF XY: 0.0774 AC XY: 56002 AN XY: 723280

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.0603

Gnomad4 ASJ exome AF: 0.0718

Gnomad4 EAS exome AF: 0.000279

Gnomad4 SAS exome AF: 0.0287

Gnomad4 FIN exome AF: 0.0366

Gnomad4 NFE exome AF: 0.0892

Gnomad4 OTH exome AF: 0.0765

GnomAD4 genome AF: 0.0617 AC: 9393 AN: 152242 Hom.: 395 Cov.: 32 AF XY: 0.0587 AC XY: 4368 AN XY: 74440

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0881

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0893 Hom.: 723

Bravo AF: 0.0654

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	20
Dann	Benign	0.82

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: rs11199005; hg19: chr10-121296029;