rs1018129727

Variant names:

• chr16-269358-G-A
• rs1018129727
• NM_183337.3:c.1315C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-269358-G-A
• chr16-269358-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183337.3(RGS11):​c.1315C>T​(p.Arg439Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,603,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: RGS11 NM_183337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

RGS11 (HGNC:9993): (regulator of G protein signaling 11) The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2013]

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286901 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20872289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183337.3. 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
	RGS11	NM_183337.3	MANE Select	c.1315C>T	p.Arg439Trp	missense	Exon 17 of 17	NP_899180.1	O94810-1
	RGS11	NM_001286485.2		c.1282C>T	p.Arg428Trp	missense	Exon 16 of 16	NP_001273414.1	O94810-2
	RGS11	NM_003834.3		c.1252C>T	p.Arg418Trp	missense	Exon 17 of 17	NP_003825.1	O94810-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS11	ENST00000397770.8	TSL:1 MANE Select	c.1315C>T	p.Arg439Trp	missense	Exon 17 of 17	ENSP00000380876.3	O94810-1
	RGS11	ENST00000359740.6	TSL:1	c.1282C>T	p.Arg428Trp	missense	Exon 16 of 16	ENSP00000352778.5	O94810-2
	RGS11	ENST00000316163.9	TSL:1	c.1252C>T	p.Arg418Trp	missense	Exon 17 of 17	ENSP00000319069.5	O94810-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000217 AC: 5 AN: 230530 AF XY: 0.0000240

Gnomad AFR exome AF: 0.0000694

Gnomad AMR exome AF: 0.0000928

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000159 AC: 23 AN: 1450866 Hom.: 0 Cov.: 31 AF XY: 0.0000153 AC XY: 11 AN XY: 720732

African (AFR) AF: 0.0000300 AC: 1 AN: 33376

American (AMR) AF: 0.0000465 AC: 2 AN: 43000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.0000163 AC: 18 AN: 1107504

Other (OTH) AF: 0.0000167 AC: 1 AN: 59956

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.084
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.11
MVP		0.70
MPC		0.10
ClinPred		0.22	T
GERP RS		-1.2
Varity_R		0.083
gMVP		0.48
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1018129727; hg19: chr16-319357;