rs397704705
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014855.3(AP5Z1):c.80_83delinsTGCTGTAAACTGTAACTGTAAA(p.Arg27_Ile28delinsLeuLeuTer) variant causes a stop gained, protein altering change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
AP5Z1
NM_014855.3 stop_gained, protein_altering
NM_014855.3 stop_gained, protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
AP5Z1 (HGNC:22197): (adaptor related protein complex 5 subunit zeta 1) This gene was identified by genome-wide screen for genes involved in homologous recombination DNA double-strand break repair (HR-DSBR). The encoded protein was found in a complex with other proteins that have a role in HR-DSBR. Knockdown of this gene reduced homologous recombination, and mutations in this gene were found in patients with spastic paraplegia. It was concluded that this gene likely encodes a helicase (PMID:20613862). [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 23 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-4781213-GGAT-TGCTGTAAACTGTAACTGTAAA is Pathogenic according to our data. Variant chr7-4781213-GGAT-TGCTGTAAACTGTAACTGTAAA is described in ClinVar as [Pathogenic]. Clinvar id is 2.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP5Z1 | NM_014855.3 | c.80_83delinsTGCTGTAAACTGTAACTGTAAA | p.Arg27_Ile28delinsLeuLeuTer | stop_gained, protein_altering_variant | 2/17 | ENST00000649063.2 | |
AP5Z1 | NM_001364858.1 | c.-202_-199delinsTGCTGTAAACTGTAACTGTAAA | 5_prime_UTR_variant | 2/16 | |||
AP5Z1 | NR_157345.1 | n.173_176delinsTGCTGTAAACTGTAACTGTAAA | non_coding_transcript_exon_variant | 2/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.80_83delinsTGCTGTAAACTGTAACTGTAAA | p.Arg27_Ile28delinsLeuLeuTer | stop_gained, protein_altering_variant | 2/17 | NM_014855.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 48 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 29, 2010 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at