rs762991211
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_001354768.3(NRL):c.91C>T(p.Arg31*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_001354768.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NRL | NM_001354768.3 | c.91C>T | p.Arg31* | stop_gained | Exon 2 of 3 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRL | ENST00000561028.6 | c.91C>T | p.Arg31* | stop_gained | Exon 2 of 3 | 2 | NM_001354768.3 | ENSP00000454062.2 | ||
NRL | ENST00000396997.1 | c.91C>T | p.Arg31* | stop_gained | Exon 3 of 4 | 1 | ENSP00000380193.1 | |||
NRL | ENST00000397002.6 | c.91C>T | p.Arg31* | stop_gained | Exon 2 of 3 | 1 | ENSP00000380197.2 | |||
NRL | ENST00000558280.1 | c.91C>T | p.Arg31* | stop_gained | Exon 3 of 3 | 5 | ENSP00000454180.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135810
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Enhanced S-cone syndrome Pathogenic:2
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Arg31*) in the NRL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NRL are known to be pathogenic (PMID: 11694879, 15591106). This variant is present in population databases (rs762991211, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with autosomal recessive NRL-related conditions (PMID: 27732723, 31456290). ClinVar contains an entry for this variant (Variation ID: 369652). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. -
Retinitis pigmentosa 27 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at