4-625681-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000283.4(PDE6B):c.55G>T(p.Ala19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000283.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDE6B | NM_000283.4 | c.55G>T | p.Ala19Ser | missense_variant | 1/22 | ENST00000496514.6 | NP_000274.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDE6B | ENST00000496514.6 | c.55G>T | p.Ala19Ser | missense_variant | 1/22 | 1 | NM_000283.4 | ENSP00000420295 | P3 | |
PDE6B | ENST00000255622.10 | c.55G>T | p.Ala19Ser | missense_variant | 1/22 | 1 | ENSP00000255622 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249712Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135132
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461594Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727118
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2021 | The c.55G>T (p.A19S) alteration is located in exon 1 (coding exon 1) of the PDE6B gene. This alteration results from a G to T substitution at nucleotide position 55, causing the alanine (A) at amino acid position 19 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 16, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 960655). This variant has not been reported in the literature in individuals affected with PDE6B-related conditions. This variant is present in population databases (rs201287238, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 19 of the PDE6B protein (p.Ala19Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at