chr1-192644344-C-T

Variant names:

• chr1-192644344-C-T
• rs531861902
• NM_002927.5:c.10C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002927.5(RGS13):​c.10C>T​(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,609,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RGS13 NM_002927.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.652
• Publications: 0 publications found

Genes affected

RGS13 (HGNC:9995): (regulator of G protein signaling 13) The protein encoded by this gene is a member of the regulator of G protein signaling (RGS) family. RGS family members share similarity with S. cerevisiae SST2 and C. elegans egl-10 proteins, which contain a characteristic conserved RGS domain. RGS proteins accelerate GTPase activity of G protein alpha-subunits, thereby driving G protein into their inactive GDP-bound form, thus negatively regulating G protein signaling. RGS proteins have been implicated in the fine tuning of a variety of cellular events in response to G protein-coupled receptor activation. The biological function of this gene, however, is unknown. Two transcript variants encoding the same isoform exist. [provided by RefSeq, Jul 2008]

RGS2-AS1 (HGNC:49018): (RSG2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03272313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002927.5. 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
	RGS13	NM_002927.5	MANE Select	c.10C>T	p.Arg4Trp	missense	Exon 4 of 7	NP_002918.1	O14921
	RGS13	NM_144766.3		c.10C>T	p.Arg4Trp	missense	Exon 3 of 6	NP_658912.1	O14921

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS13	ENST00000391995.7	TSL:1 MANE Select	c.10C>T	p.Arg4Trp	missense	Exon 4 of 7	ENSP00000375853.2	O14921
	RGS13	ENST00000543215.5	TSL:1	c.10C>T	p.Arg4Trp	missense	Exon 3 of 6	ENSP00000442837.1	O14921
	RGS13	ENST00000462955.1	TSL:1	n.258C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151852 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 249880 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1457046 Hom.: 0 Cov.: 28 AF XY: 0.0000193 AC XY: 14 AN XY: 724970

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.0000224 AC: 1 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39496

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85652

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108656

Other (OTH) AF: 0.0000166 AC: 1 AN: 60178

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151970 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74226

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.000131 AC: 2 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.65
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.086
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.40		Loss of disorder (P = 0)
MVP		0.56
MPC		0.032
ClinPred		0.13	T
GERP RS		-0.79
Varity_R		0.064
gMVP		0.33
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs531861902; hg19: chr1-192613474; COSMIC: COSV101232296; COSMIC: COSV101232296;