14-67729196-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152443.3(RDH12):c.664G>T(p.Gly222Trp) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★).
Frequency
Consequence
NM_152443.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RDH12 | NM_152443.3 | c.664G>T | p.Gly222Trp | missense_variant | Exon 8 of 9 | ENST00000551171.6 | NP_689656.2 | |
RDH12 | XM_047430965.1 | c.664G>T | p.Gly222Trp | missense_variant | Exon 8 of 9 | XP_047286921.1 | ||
ZFYVE26 | XM_047431173.1 | c.*546C>A | 3_prime_UTR_variant | Exon 42 of 42 | XP_047287129.1 | |||
GPHN | XM_047430879.1 | c.1313-5999G>T | intron_variant | Intron 14 of 14 | XP_047286835.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RDH12 | ENST00000551171.6 | c.664G>T | p.Gly222Trp | missense_variant | Exon 8 of 9 | 1 | NM_152443.3 | ENSP00000449079.1 | ||
RDH12 | ENST00000267502.3 | c.664G>T | p.Gly222Trp | missense_variant | Exon 7 of 8 | 5 | ENSP00000267502.3 | |||
RDH12 | ENST00000552873.1 | n.33G>T | non_coding_transcript_exon_variant | Exon 2 of 2 | 5 | |||||
ZFYVE26 | ENST00000394455.6 | n.3288+15C>A | intron_variant | Intron 14 of 14 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248940Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134834
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Leber congenital amaurosis 13 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RDH12 protein function. This variant has not been reported in the literature in individuals affected with RDH12-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 222 of the RDH12 protein (p.Gly222Trp). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at