rs3009907

Positions:

• chr10-119502942-G-T

Variant summary

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

The NM_001005339.2(RGS10):​c.400-2683C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,134 control chromosomes in the GnomAD database, including 1,558 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 0.13 (1558 hom., cov: 31)
• Consequence: RGS10 NM_001005339.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS10	NM_001005339.2	c.400-2683C>A		intron_variant		ENST00000369103.3
RGS10	NM_002925.4	c.358-2683C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS10	ENST00000369103.3	c.400-2683C>A		intron_variant		1	NM_001005339.2	P1
RGS10	ENST00000369101.7	c.376-2683C>A		intron_variant		1
RGS10	ENST00000392865.5	c.358-2683C>A		intron_variant		1
RGS10	ENST00000469575.1	n.137-2683C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19245 AN: 152016 Hom.: 1555 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19268 AN: 152134 Hom.: 1558 Cov.: 31 AF XY: 0.124 AC XY: 9238 AN XY: 74356

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.125

Alfa AF: 0.103 Hom.: 1429

Bravo AF: 0.139

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.92

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: rs3009907; hg19: chr10-121262454;