rs116139296
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015346.4(ZFYVE26):āc.3847A>Gā(p.Thr1283Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. T1283T) has been classified as Likely benign.
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.3847A>G | p.Thr1283Ala | missense_variant | 21/42 | ENST00000347230.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.3847A>G | p.Thr1283Ala | missense_variant | 21/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251170Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135712
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1460966Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 726606
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 27, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1283 of the ZFYVE26 protein (p.Thr1283Ala). This variant is present in population databases (rs116139296, gnomAD 0.1%). 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: 458282). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | Aug 02, 2021 | The c.3847A>G (p.T1283A) alteration is located in exon 21 (coding exon 20) of the ZFYVE26 gene. This alteration results from a A to G substitution at nucleotide position 3847, causing the threonine (T) at amino acid position 1283 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at