chr5-78113889-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_003664.5(AP3B1):c.2112C>T(p.Gly704=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,613,960 control chromosomes in the GnomAD database, including 1 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 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )
Consequence
AP3B1
NM_003664.5 synonymous
NM_003664.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.94
Genes affected
AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 5-78113889-G-A is Benign according to our data. Variant chr5-78113889-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 533472.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.94 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00181 (276/152110) while in subpopulation AFR AF= 0.00634 (263/41482). AF 95% confidence interval is 0.00571. There are 1 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| AP3B1 | NM_003664.5 | c.2112C>T | p.Gly704= | synonymous_variant | 19/27 | ENST00000255194.11 | NP_003655.3 | |
| AP3B1 | NM_001271769.2 | c.1965C>T | p.Gly655= | synonymous_variant | 19/27 | NP_001258698.1 | ||
| AP3B1 | NM_001410752.1 | c.2112C>T | p.Gly704= | synonymous_variant | 19/23 | NP_001397681.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AP3B1 | ENST00000255194.11 | c.2112C>T | p.Gly704= | synonymous_variant | 19/27 | 1 | NM_003664.5 | ENSP00000255194 | P2 |
Frequencies
GnomAD3 genomes 0.00181 AC: 275AN: 151992Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000450 AC: 113AN: 251216Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135786
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GnomAD4 exome AF: 0.000236 AC: 345AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.000184 AC XY: 134AN XY: 727224
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GnomAD4 genome 0.00181 AC: 276AN: 152110Hom.: 1 Cov.: 32 AF XY: 0.00151 AC XY: 112AN XY: 74342
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autoinflammatory syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 02, 2018 | - - |
Hermansky-Pudlak syndrome 2 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
AP3B1-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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