chr14-67755987-GTTC-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_015346.4(ZFYVE26):c.6744_6746delGAA(p.Lys2248del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015346.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.6744_6746delGAA | p.Lys2248del | disruptive_inframe_deletion | Exon 36 of 42 | ENST00000347230.9 | NP_056161.2 | |
ZFYVE26 | XM_047431173.1 | c.6744_6746delGAA | p.Lys2248del | disruptive_inframe_deletion | Exon 36 of 42 | XP_047287129.1 | ||
ZFYVE26 | XM_047431174.1 | c.4419_4421delGAA | p.Lys1473del | disruptive_inframe_deletion | Exon 25 of 31 | XP_047287130.1 | ||
ZFYVE26 | XM_047431175.1 | c.4326_4328delGAA | p.Lys1442del | disruptive_inframe_deletion | Exon 25 of 31 | XP_047287131.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251448Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135888
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461892Hom.: 0 AF XY: 0.0000165 AC XY: 12AN XY: 727246
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74508
ClinVar
Submissions by phenotype
not provided Pathogenic:1
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36315648, 24833714, 37681008) -
Spastic paraplegia Uncertain:1
This variant, c.6744_6746del, results in the deletion of 1 amino acid(s) of the ZFYVE26 protein (p.Lys2248del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs764479245, gnomAD 0.007%). This variant has been observed in individual(s) with complicated spastic paraplegia (PMID: 24833714). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 241056). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Hereditary spastic paraplegia 15 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at