rs1555961989
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001034853.2(RPGR):c.1826A>G(p.Asn609Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 21)
Consequence
RPGR
NM_001034853.2 missense
NM_001034853.2 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: -0.00100
Genes affected
RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08301669).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGR | NM_001034853.2 | c.1826A>G | p.Asn609Ser | missense_variant | 15/15 | ENST00000645032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000645032.1 | c.1826A>G | p.Asn609Ser | missense_variant | 15/15 | NM_001034853.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD3 genomes
?
Cov.:
21
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 21
GnomAD4 genome
?
Cov.:
21
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 609 of the RPGR protein (p.Asn609Ser). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 454513). This variant has not been reported in the literature in individuals affected with RPGR-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;.;N
REVEL
Benign
Sift
Benign
T;.;T;.;.;.
Sift4G
Benign
T;.;T;.;.;T
Polyphen
B;B;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at N609 (P = 0.0208);Gain of phosphorylation at N609 (P = 0.0208);.;.;Gain of phosphorylation at N609 (P = 0.0208);Gain of phosphorylation at N609 (P = 0.0208);
MVP
MPC
0.020
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at