rs199702315
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_003664.5(AP3B1):c.2409_2411del(p.Lys804del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,523,058 control chromosomes in the GnomAD database, including 294 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 28 hom., cov: 32)
Exomes 𝑓: 0.018 ( 266 hom. )
Consequence
AP3B1
NM_003664.5 inframe_deletion
NM_003664.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.78
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 -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_003664.5. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 5-78101011-TTTC-T is Benign according to our data. Variant chr5-78101011-TTTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 179635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78101011-TTTC-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2162/152258) while in subpopulation NFE AF= 0.02 (1358/67960). AF 95% confidence interval is 0.0191. There are 28 homozygotes in gnomad4. There are 1056 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP3B1 | NM_003664.5 | c.2409_2411del | p.Lys804del | inframe_deletion | 21/27 | ENST00000255194.11 | |
AP3B1 | NM_001271769.2 | c.2262_2264del | p.Lys755del | inframe_deletion | 21/27 | ||
AP3B1 | NM_001410752.1 | c.2409_2411del | p.Lys804del | inframe_deletion | 21/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP3B1 | ENST00000255194.11 | c.2409_2411del | p.Lys804del | inframe_deletion | 21/27 | 1 | NM_003664.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0142 AC: 2165AN: 152140Hom.: 28 Cov.: 32
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GnomAD3 exomes AF: 0.0136 AC: 3069AN: 226264Hom.: 36 AF XY: 0.0133 AC XY: 1621AN XY: 121804
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GnomAD4 exome AF: 0.0175 AC: 24053AN: 1370800Hom.: 266 AF XY: 0.0172 AC XY: 11757AN XY: 684740
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GnomAD4 genome ? AF: 0.0142 AC: 2162AN: 152258Hom.: 28 Cov.: 32 AF XY: 0.0142 AC XY: 1056AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 10, 2014 | Lys804del in exon 21 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 1.85% (161/8721) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs199702315). - |
Hermansky-Pudlak syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hermansky-Pudlak syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 24, 2020 | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 19, 2022 | - - |
Computational scores
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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