rs1057519271
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001278512.2(AP3B2):c.2579_2582del(p.Leu860GlnfsTer10) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000206 in 1,459,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000021 ( 0 hom. )
Consequence
AP3B2
NM_001278512.2 frameshift
NM_001278512.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.36
Genes affected
AP3B2 (HGNC:567): (adaptor related protein complex 3 subunit beta 2) Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]
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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 15-82663148-TGTGA-T is Pathogenic according to our data. Variant chr15-82663148-TGTGA-T is described in ClinVar as [Pathogenic]. Clinvar id is 374849.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP3B2 | NM_001278512.2 | c.2579_2582del | p.Leu860GlnfsTer10 | frameshift_variant | 22/27 | ENST00000535359.6 | |
CPEB1-AS1 | NR_046096.1 | n.1328+13006_1328+13009del | intron_variant, non_coding_transcript_variant | ||||
AP3B2 | NM_001278511.2 | c.2426_2429del | p.Leu809GlnfsTer10 | frameshift_variant | 20/25 | ||
AP3B2 | NM_004644.5 | c.2522_2525del | p.Leu841GlnfsTer10 | frameshift_variant | 21/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP3B2 | ENST00000535359.6 | c.2579_2582del | p.Leu860GlnfsTer10 | frameshift_variant | 22/27 | 1 | NM_001278512.2 | ||
CPEB1-AS1 | ENST00000560650.1 | n.1328+13006_1328+13009del | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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?
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GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247438Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134280
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459534Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725956
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 48 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 19, 2020 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at