chr7-4781259-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_014855.3(AP5Z1):c.126C>T(p.Leu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000566 in 1,613,848 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0030 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 3 hom. )
Consequence
AP5Z1
NM_014855.3 synonymous
NM_014855.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.30
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 7-4781259-C-T is Benign according to our data. Variant chr7-4781259-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 446846.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}. Variant chr7-4781259-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.3 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| AP5Z1 | NM_014855.3 | c.126C>T | p.Leu42= | synonymous_variant | 2/17 | ENST00000649063.2 | NP_055670.1 | |
| AP5Z1 | NM_001364858.1 | c.-156C>T | 5_prime_UTR_variant | 2/16 | NP_001351787.1 | |||
| AP5Z1 | NR_157345.1 | n.219C>T | non_coding_transcript_exon_variant | 2/17 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AP5Z1 | ENST00000649063.2 | c.126C>T | p.Leu42= | synonymous_variant | 2/17 | NM_014855.3 | ENSP00000497815 | P1 |
Frequencies
GnomAD3 genomes 0.00295 AC: 449AN: 152198Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000947 AC: 236AN: 249192Hom.: 1 AF XY: 0.000777 AC XY: 105AN XY: 135210
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GnomAD4 exome AF: 0.000316 AC: 462AN: 1461532Hom.: 3 Cov.: 31 AF XY: 0.000294 AC XY: 214AN XY: 727046
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GnomAD4 genome 0.00297 AC: 452AN: 152316Hom.: 1 Cov.: 33 AF XY: 0.00283 AC XY: 211AN XY: 74476
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 48 Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 16, 2016 | - - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at