rs606231423
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_016026.4(RDH11):c.199C>T(p.Arg67Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000955 in 1,570,784 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000092 ( 0 hom. )
Consequence
RDH11
NM_016026.4 stop_gained
NM_016026.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 3.74
Genes affected
RDH11 (HGNC:17964): (retinol dehydrogenase 11) Enables NADP-retinol dehydrogenase activity. Involved in cellular detoxification of aldehyde and retinoid metabolic process. Acts upstream of or within retinal metabolic process. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 14-67692588-G-A is Pathogenic according to our data. Variant chr14-67692588-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 161115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RDH11 | NM_016026.4 | c.199C>T | p.Arg67Ter | stop_gained | 3/7 | ENST00000381346.9 | |
RDH11 | NM_001252650.2 | c.199C>T | p.Arg67Ter | stop_gained | 3/6 | ||
GPHN | XM_047430879.1 | c.1313-42607G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RDH11 | ENST00000381346.9 | c.199C>T | p.Arg67Ter | stop_gained | 3/7 | 1 | NM_016026.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000143 AC: 3AN: 209610Hom.: 0 AF XY: 0.00000885 AC XY: 1AN XY: 113028
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GnomAD4 exome AF: 0.00000916 AC: 13AN: 1418720Hom.: 0 Cov.: 31 AF XY: 0.00000853 AC XY: 6AN XY: 703216
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2014 | - - |
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Nov 01, 2014 | This variant was found in trans with pathogenic variant NM_016026.3:c.322C>T in three compound heterozygotes with retinal dystrophy, juvenile cataracts, and short stature syndrome - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 161115). This premature translational stop signal has been observed in individual(s) with syndromic retinal dystrophy (PMID: 24916380). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs606231423, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg67*) in the RDH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RDH11 are known to be pathogenic (PMID: 24916380). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
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