rs532059976
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015346.4(ZFYVE26):c.2615G>A(p.Arg872His) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R872C) has been classified 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.2615G>A | p.Arg872His | missense_variant | 15/42 | ENST00000347230.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.2615G>A | p.Arg872His | missense_variant | 15/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251474Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727240
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74458
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2021 | This sequence change replaces arginine with histidine at codon 872 of the ZFYVE26 protein (p.Arg872His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs532059976, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with ZFYVE26-related conditions. 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: "Possibly Damaging"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at