rs374390376
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PM1PM2PP5_Very_Strong
The NM_174878.3(CLRN1):c.92C>T(p.Pro31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31R) has been classified as Uncertain significance.
Frequency
Consequence
NM_174878.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Retinitis pigmentosa 61 Pathogenic:1
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not provided Pathogenic:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 31 of the CLRN1 protein (p.Pro31Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 21310491). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30575). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CLRN1 function (PMID: 21310491). For these reasons, this variant has been classified as Pathogenic. -
Retinal dystrophy Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at