14-24081237-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4
The NM_001354768.3(NRL):c.713G>T(p.Ter238LeuextTer58) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,337,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000060 ( 0 hom. )
Consequence
NRL
NM_001354768.3 stop_lost
NM_001354768.3 stop_lost
Scores
3
4
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
NRL (HGNC:8002): (neural retina leucine zipper) This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM4
Stoplost variant in NM_001354768.3 Downstream stopcodon found after 110 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NRL | NM_001354768.3 | c.713G>T | p.Ter238LeuextTer58 | stop_lost | 3/3 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRL | ENST00000561028.6 | c.713G>T | p.Ter238LeuextTer58 | stop_lost | 3/3 | 2 | NM_001354768.3 | ENSP00000454062 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000866 AC: 1AN: 115494Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 63964
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GnomAD4 exome AF: 0.00000598 AC: 8AN: 1337952Hom.: 0 Cov.: 31 AF XY: 0.00000757 AC XY: 5AN XY: 660188
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Apr 01, 2021 | The p.Ter238LeuextTer58 variant in NRL was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PM4. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab. - |
Pathogenic, no assertion criteria provided | research | Leeds Institute of Medical Research, University of Leeds | Jan 15, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
N;N;N;N;N
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at