14-67786228-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015346.4(ZFYVE26):āc.3025C>Gā(p.Arg1009Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 1,293,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1009W) 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.3025C>G | p.Arg1009Gly | missense_variant | 17/42 | ENST00000347230.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.3025C>G | p.Arg1009Gly | missense_variant | 17/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000570 AC: 7AN: 122894Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000171 AC: 4AN: 234122Hom.: 0 AF XY: 0.00000788 AC XY: 1AN XY: 126972
GnomAD4 exome AF: 0.00000171 AC: 2AN: 1170362Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0AN XY: 585412
GnomAD4 genome AF: 0.0000570 AC: 7AN: 122894Hom.: 0 Cov.: 30 AF XY: 0.0000708 AC XY: 4AN XY: 56510
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1009 of the ZFYVE26 protein (p.Arg1009Gly). This variant is present in population databases (rs374605354, gnomAD 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: "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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at