rs116733939
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_152443.3(RDH12):c.524C>A(p.Ser175Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S175S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_152443.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RDH12 | NM_152443.3 | c.524C>A | p.Ser175Ter | stop_gained | 7/9 | ENST00000551171.6 | |
RDH12 | XM_047430965.1 | c.524C>A | p.Ser175Ter | stop_gained | 7/9 | ||
GPHN | XM_047430879.1 | c.1313-8139C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RDH12 | ENST00000551171.6 | c.524C>A | p.Ser175Ter | stop_gained | 7/9 | 1 | NM_152443.3 | P1 | |
RDH12 | ENST00000267502.3 | c.524C>A | p.Ser175Ter | stop_gained | 6/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Leber congenital amaurosis 13 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 26, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RDH12 are known to be pathogenic (PMID: 17964524, 22065924). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RDH12-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser175*) in the RDH12 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.