chr7-4781029-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014855.3(AP5Z1):c.42-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,062,410 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0090 ( 20 hom., cov: 33)
Exomes 𝑓: 0.00089 ( 13 hom. )
Consequence
AP5Z1
NM_014855.3 intron
NM_014855.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.108
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 7-4781029-C-T is Benign according to our data. Variant chr7-4781029-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1178374.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00904 (1376/152294) while in subpopulation AFR AF= 0.0314 (1305/41556). AF 95% confidence interval is 0.03. There are 20 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP5Z1 | NM_014855.3 | c.42-146C>T | intron_variant | ENST00000649063.2 | |||
AP5Z1 | NM_001364858.1 | c.-240-146C>T | intron_variant | ||||
AP5Z1 | NR_157345.1 | n.135-146C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.42-146C>T | intron_variant | NM_014855.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00905 AC: 1377AN: 152176Hom.: 20 Cov.: 33
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GnomAD4 exome AF: 0.000891 AC: 811AN: 910116Hom.: 13 AF XY: 0.000791 AC XY: 358AN XY: 452522
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GnomAD4 genome ? AF: 0.00904 AC: 1376AN: 152294Hom.: 20 Cov.: 33 AF XY: 0.00898 AC XY: 669AN XY: 74468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 10, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at