rs138965635
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015346.4(ZFYVE26):c.5401G>A(p.Ala1801Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000722 in 1,613,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. A1801G) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.5401G>A | p.Ala1801Thr | missense_variant | 28/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.5401G>A | p.Ala1801Thr | missense_variant | 28/42 | ||
ZFYVE26 | XM_047431174.1 | c.3076G>A | p.Ala1026Thr | missense_variant | 17/31 | ||
ZFYVE26 | XM_047431175.1 | c.2983G>A | p.Ala995Thr | missense_variant | 17/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.5401G>A | p.Ala1801Thr | missense_variant | 28/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000546 AC: 83AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000377 AC: 94AN: 249342Hom.: 0 AF XY: 0.000379 AC XY: 51AN XY: 134668
GnomAD4 exome AF: 0.000740 AC: 1081AN: 1460940Hom.: 0 Cov.: 32 AF XY: 0.000694 AC XY: 504AN XY: 726674
GnomAD4 genome ? AF: 0.000545 AC: 83AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000511 AC XY: 38AN XY: 74380
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 15 Uncertain:2Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 12-16-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 16, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 16, 2021 | - - |
not provided Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 24, 2022 | BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1801 of the ZFYVE26 protein (p.Ala1801Thr). This variant is present in population databases (rs138965635, gnomAD 0.07%). 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: 241050). 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"). 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