NM_001278512.2:c.2579_2582delTCAC
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001278512.2(AP3B2):c.2579_2582delTCAC(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
Publications
0 publications found
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 was made for transcript
Our verdict: Pathogenic. The variant received 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 VariationId is 374849.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001278512.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AP3B2 | MANE Select | c.2579_2582delTCAC | p.Leu860GlnfsTer10 | frameshift | Exon 22 of 27 | NP_001265441.1 | Q13367-4 | ||
| AP3B2 | c.2522_2525delTCAC | p.Leu841GlnfsTer10 | frameshift | Exon 21 of 26 | NP_004635.2 | ||||
| AP3B2 | c.2426_2429delTCAC | p.Leu809GlnfsTer10 | frameshift | Exon 20 of 25 | NP_001265440.1 | Q13367-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AP3B2 | TSL:1 MANE Select | c.2579_2582delTCAC | p.Leu860GlnfsTer10 | frameshift | Exon 22 of 27 | ENSP00000440984.1 | Q13367-4 | ||
| AP3B2 | TSL:1 | c.2540_2543delTCAC | p.Leu847GlnfsTer10 | frameshift | Exon 21 of 26 | ENSP00000261722.4 | A0A5F9UJV3 | ||
| AP3B2 | TSL:1 | c.2426_2429delTCAC | p.Leu809GlnfsTer10 | frameshift | Exon 20 of 25 | ENSP00000438721.1 | Q13367-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000808 AC: 2AN: 247438 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
247438
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459534Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725956 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1459534
Hom.:
AF XY:
AC XY:
1
AN XY:
725956
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33412
American (AMR)
AF:
AC:
0
AN:
44630
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26110
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
85866
European-Finnish (FIN)
AF:
AC:
0
AN:
53380
Middle Eastern (MID)
AF:
AC:
0
AN:
4774
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111456
Other (OTH)
AF:
AC:
0
AN:
60224
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
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ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Developmental and epileptic encephalopathy, 48 (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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