rs786205509

Variant names:

• chr17-65190194-C-G
• rs786205509
• NM_003835.4:c.704C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-65190194-C-G
• chr17-65190194-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM5

The NM_003835.4(RGS9):​c.704C>G​(p.Ala235Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A235V) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS9 NM_003835.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• 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: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-65190194-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 191085.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS9	NM_003835.4	c.704C>G	p.Ala235Gly	missense_variant	Exon 11 of 19	ENST00000262406.10	NP_003826.2
RGS9	NM_001081955.3	c.695C>G	p.Ala232Gly	missense_variant	Exon 11 of 19		NP_001075424.1
RGS9	NM_001165933.2	c.695C>G	p.Ala232Gly	missense_variant	Exon 11 of 17		NP_001159405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000262406.10	c.704C>G	p.Ala235Gly	missense_variant	Exon 11 of 19	1	NM_003835.4	ENSP00000262406.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T;.;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	.;.;.;M
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	.;.;D;D
REVEL	Benign	0.22
Sift	Benign	0.068	.;.;T;D
Sift4G	Uncertain	0.024	.;D;D;D
Polyphen		0.97, 0.98	.;.;D;D
Vest4		0.67, 0.69, 0.60
MutPred		0.67		Gain of disorder (P = 0.1143);.;.;Gain of disorder (P = 0.1143);
MVP		0.67
MPC		0.62
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.83
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs786205509; hg19: chr17-63186312;