rs117250367
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015346.4(ZFYVE26):āc.5714C>Gā(p.Ala1905Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,614,108 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 (ā ā ).
Frequency
Consequence
NM_015346.4 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 |
---|---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.5714C>G | p.Ala1905Gly | missense_variant | 31/42 | ENST00000347230.9 | NP_056161.2 | |
ZFYVE26 | XM_047431173.1 | c.5714C>G | p.Ala1905Gly | missense_variant | 31/42 | XP_047287129.1 | ||
ZFYVE26 | XM_047431174.1 | c.3389C>G | p.Ala1130Gly | missense_variant | 20/31 | XP_047287130.1 | ||
ZFYVE26 | XM_047431175.1 | c.3296C>G | p.Ala1099Gly | missense_variant | 20/31 | XP_047287131.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.5714C>G | p.Ala1905Gly | missense_variant | 31/42 | 1 | NM_015346.4 | ENSP00000251119 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152102Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251360Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135848
GnomAD4 exome AF: 0.000194 AC: 284AN: 1461888Hom.: 0 Cov.: 30 AF XY: 0.000215 AC XY: 156AN XY: 727244
GnomAD4 genome AF: 0.000131 AC: 20AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 8AN XY: 74434
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 29, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1905 of the ZFYVE26 protein (p.Ala1905Gly). This variant is present in population databases (rs117250367, gnomAD 0.02%). 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: 458288). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | GeneDx | Nov 16, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at