rs199969454
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015346.4(ZFYVE26):c.686C>A(p.Ala229Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015346.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.686C>A | p.Ala229Glu | missense_variant | 5/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.686C>A | p.Ala229Glu | missense_variant | 5/42 | ||
ZFYVE26 | XM_011536609.3 | c.686C>A | p.Ala229Glu | missense_variant | 5/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.686C>A | p.Ala229Glu | missense_variant | 5/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251308Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727240
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 229 of the ZFYVE26 protein (p.Ala229Glu). This variant is present in population databases (rs199969454, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ZFYVE26-related conditions. ClinVar contains an entry for this variant (Variation ID: 130784). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 06, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at