rs1057519342
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014855.3(AP5Z1):c.1732C>T(p.Gln578Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AP5Z1
NM_014855.3 stop_gained
NM_014855.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 1.67
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 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-4789856-C-T is Pathogenic according to our data. Variant chr7-4789856-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375316.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP5Z1 | NM_014855.3 | c.1732C>T | p.Gln578Ter | stop_gained | 14/17 | ENST00000649063.2 | NP_055670.1 | |
AP5Z1 | NM_001364858.1 | c.1264C>T | p.Gln422Ter | stop_gained | 13/16 | NP_001351787.1 | ||
AP5Z1 | XM_047421098.1 | c.1396C>T | p.Gln466Ter | stop_gained | 12/15 | XP_047277054.1 | ||
AP5Z1 | NR_157345.1 | n.1863C>T | non_coding_transcript_exon_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.1732C>T | p.Gln578Ter | stop_gained | 14/17 | NM_014855.3 | ENSP00000497815 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1400508Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 691094
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1400508
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
691094
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 48 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 26, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at