chr17-65190194-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_003835.4(RGS9):c.704C>T(p.Ala235Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RGS9
NM_003835.4 missense
NM_003835.4 missense
Scores
2
7
5
Clinical Significance
Conservation
PhyloP100: 3.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-65190194-C-T is Pathogenic according to our data. Variant chr17-65190194-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191085.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-65190194-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGS9 | NM_003835.4 | c.704C>T | p.Ala235Val | missense_variant | 11/19 | ENST00000262406.10 | |
RGS9 | NM_001081955.3 | c.695C>T | p.Ala232Val | missense_variant | 11/19 | ||
RGS9 | NM_001165933.2 | c.695C>T | p.Ala232Val | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGS9 | ENST00000262406.10 | c.704C>T | p.Ala235Val | missense_variant | 11/19 | 1 | NM_003835.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461316Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727016
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Polyphen
0.99, 0.99
.;.;D;D
Vest4
0.50, 0.52, 0.74
MutPred
Gain of MoRF binding (P = 0.1524);.;.;Gain of MoRF binding (P = 0.1524);
MVP
0.62
MPC
0.33
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at