NM_003835.4:c.1502G>T

Variant names:

• chr17-65225096-G-T
• rs34797451
• NM_003835.4:c.1502G>T

Variant summary

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

The NM_003835.4(RGS9):​c.1502G>T​(p.Arg501Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R501H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS9 NM_003835.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.604
• Publications: 0 publications found

Genes affected

RGS9 (HGNC:10004): (regulator of G protein signaling 9) This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G proteins in the rod and cone phototransduction cascades. Mutations in this gene result in bradyopsia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

RGS9 Gene-Disease associations (from GenCC):

• prolonged electroretinal response suppression 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• bradyopsia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

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_003835.4. 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
	RGS9	NM_003835.4	MANE Select	c.1502G>T	p.Arg501Leu	missense	Exon 18 of 19	NP_003826.2	O75916-1
	RGS9	NM_001081955.3		c.1493G>T	p.Arg498Leu	missense	Exon 18 of 19	NP_001075424.1	O75916-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	ENST00000262406.10	TSL:1 MANE Select	c.1502G>T	p.Arg501Leu	missense	Exon 18 of 19	ENSP00000262406.9	O75916-1
	RGS9	ENST00000449996.7	TSL:1	c.1493G>T	p.Arg498Leu	missense	Exon 18 of 19	ENSP00000396329.3	O75916-5
	RGS9	ENST00000443584.7	TSL:1	c.1493G>T	p.Arg498Leu	missense	Exon 18 of 18	ENSP00000405814.3	E9PD91

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0038
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.60
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.096	T
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.27		Loss of MoRF binding (P = 0.0089)
MVP		0.55
MPC		0.31
ClinPred		0.61	D
GERP RS		3.9
Varity_R		0.19
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 10

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

Other links and lift over

dbSNP: rs34797451; hg19: chr17-63221214;