3-129528766-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000539.3(RHO):c.36del(p.Phe13SerfsTer35) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000031 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RHO
NM_000539.3 frameshift
NM_000539.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
RHO (HGNC:10012): (rhodopsin) The protein encoded by this gene is found in rod cells in the back of the eye and is essential for vision in low-light conditions. The encoded protein binds to 11-cis retinal and is activated when light hits the retinal molecule. Defects in this gene are a cause of congenital stationary night blindness. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 517 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-129528766-GC-G is Pathogenic according to our data. Variant chr3-129528766-GC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1456255.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Uncertain_significance=1}. Variant chr3-129528766-GC-G is described in Lovd as [Likely_pathogenic]. Variant chr3-129528766-GC-G is described in Lovd as [Pathogenic]. Variant chr3-129528766-GC-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHO | NM_000539.3 | c.36del | p.Phe13SerfsTer35 | frameshift_variant | 1/5 | ENST00000296271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHO | ENST00000296271.4 | c.36del | p.Phe13SerfsTer35 | frameshift_variant | 1/5 | 1 | NM_000539.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727242
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2020 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects RHO protein function (PMID: 30977563). This variant has been reported in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 26161267, 31319082); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe13Serfs*35) in the RHO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RHO are known to be pathogenic (PMID: 1303237, 21174529). - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at