10-119526036-G-C

Variant names:

• chr10-119526036-G-C
• rs201021693
• NM_001005339.2:c.251C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005339.2(RGS10):​c.251C>G​(p.Thr84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/26 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T84M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RGS10 NM_001005339.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005339.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS10	NM_001005339.2	MANE Select	c.251C>G	p.Thr84Arg	missense	Exon 3 of 5	NP_001005339.1	O43665-3
	RGS10	NM_002925.4		c.209C>G	p.Thr70Arg	missense	Exon 3 of 5	NP_002916.1	O43665-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS10	ENST00000369103.3	TSL:1 MANE Select	c.251C>G	p.Thr84Arg	missense	Exon 3 of 5	ENSP00000358099.2	O43665-3
	RGS10	ENST00000369101.7	TSL:1	c.227C>G	p.Thr76Arg	missense	Exon 2 of 4	ENSP00000358097.3	O43665-1
	RGS10	ENST00000392865.5	TSL:1	c.209C>G	p.Thr70Arg	missense	Exon 3 of 5	ENSP00000376605.1	O43665-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396166 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 695824

African (AFR) AF: 0.00 AC: 0 AN: 31378

American (AMR) AF: 0.0000265 AC: 1 AN: 37754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 38736

South Asian (SAS) AF: 0.00 AC: 0 AN: 77132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069610

Other (OTH) AF: 0.00 AC: 0 AN: 57958

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.025	N
PhyloP100		2.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.055
Sift	Benign	0.16	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.33		Loss of ubiquitination at K81 (P = 0.0304)
MVP		0.17
MPC		0.80
ClinPred		0.16	T
GERP RS		3.4
Varity_R		0.057
gMVP		0.60
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 0
DS_DL_spliceai		0.34		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201021693; hg19: chr10-121285548;