rs1214483973
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015346.4(ZFYVE26):c.5215C>T(p.Arg1739Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015346.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.5215C>T | p.Arg1739Ter | stop_gained | 26/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.5215C>T | p.Arg1739Ter | stop_gained | 26/42 | ||
ZFYVE26 | XM_047431174.1 | c.2890C>T | p.Arg964Ter | stop_gained | 15/31 | ||
ZFYVE26 | XM_047431175.1 | c.2797C>T | p.Arg933Ter | stop_gained | 15/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.5215C>T | p.Arg1739Ter | stop_gained | 26/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251328Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135856
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727240
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Spastic paraplegia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change creates a premature translational stop signal (p.Arg1739*) in the ZFYVE26 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZFYVE26 are known to be pathogenic (PMID: 18394578, 19805727). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23733235). ClinVar contains an entry for this variant (Variation ID: 555771). For these reasons, this variant has been classified as Pathogenic. - |
Hereditary spastic paraplegia 15 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Dec 28, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at