rs374156343
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP3PP5
The NM_000283.4(PDE6B):c.811G>A(p.Glu271Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,906 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E271G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000283.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE6B | NM_000283.4 | c.811G>A | p.Glu271Lys | missense_variant | 4/22 | ENST00000496514.6 | |
PDE6B-AS1 | NR_183810.1 | n.140C>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE6B | ENST00000496514.6 | c.811G>A | p.Glu271Lys | missense_variant | 4/22 | 1 | NM_000283.4 | P3 | |
PDE6B-AS1 | ENST00000468356.3 | n.1302C>T | non_coding_transcript_exon_variant | 3/4 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251076Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135854
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461552Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727090
GnomAD4 genome ? AF: 0.0000656 AC: 10AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74494
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 06, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | This variant is present in population databases (rs374156343, gnomAD 0.03%). For these reasons, this variant has been classified as Pathogenic. 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 PDE6B protein function. ClinVar contains an entry for this variant (Variation ID: 497466). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 27353947, 30646425; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 271 of the PDE6B protein (p.Glu271Lys). - |
Retinal dystrophy Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Mar 07, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at