rs752388667
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015346.4(ZFYVE26):c.4955C>T(p.Ala1652Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,796 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A1652A) has been classified as Likely benign.
Frequency
Consequence
NM_015346.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.4955C>T | p.Ala1652Val | missense_variant | 25/42 | ENST00000347230.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.4955C>T | p.Ala1652Val | missense_variant | 25/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251458Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135900
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461792Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15AN XY: 727190
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74236
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1652 of the ZFYVE26 protein (p.Ala1652Val). This variant is present in population databases (rs752388667, gnomAD 0.04%). 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: 499727). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.4955C>T (p.A1652V) alteration is located in exon 25 (coding exon 24) of the ZFYVE26 gene. This alteration results from a C to T substitution at nucleotide position 4955, causing the alanine (A) at amino acid position 1652 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 03, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 25, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at