8-54621037-CT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006269.2(RP1):c.72delT(p.Arg25AlafsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_006269.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RP1 | ENST00000220676.2 | c.72delT | p.Arg25AlafsTer3 | frameshift_variant | Exon 2 of 4 | 1 | NM_006269.2 | ENSP00000220676.1 | ||
RP1 | ENST00000637698.1 | c.72delT | p.Arg25AlafsTer3 | frameshift_variant | Exon 2 of 29 | 5 | ENSP00000490104.1 | |||
RP1 | ENST00000636932.1 | c.72delT | p.Arg25AlafsTer3 | frameshift_variant | Exon 2 of 23 | 5 | ENSP00000489857.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Arg25Alafs*3) in the RP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RP1 are known to be pathogenic (PMID: 11960024, 19933189). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1424798). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at