5-78110280-A-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000255194.11(AP3B1):c.2324T>A(p.Ile775Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,609,122 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I775T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000255194.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP3B1 | NM_003664.5 | c.2324T>A | p.Ile775Lys | missense_variant | 20/27 | ENST00000255194.11 | NP_003655.3 | |
AP3B1 | NM_001271769.2 | c.2177T>A | p.Ile726Lys | missense_variant | 20/27 | NP_001258698.1 | ||
AP3B1 | NM_001410752.1 | c.2324T>A | p.Ile775Lys | missense_variant | 20/23 | NP_001397681.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP3B1 | ENST00000255194.11 | c.2324T>A | p.Ile775Lys | missense_variant | 20/27 | 1 | NM_003664.5 | ENSP00000255194 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00671 AC: 1022AN: 152198Hom.: 10 Cov.: 32
GnomAD3 exomes AF: 0.00175 AC: 427AN: 243744Hom.: 4 AF XY: 0.00128 AC XY: 168AN XY: 131528
GnomAD4 exome AF: 0.000624 AC: 909AN: 1456806Hom.: 5 Cov.: 29 AF XY: 0.000529 AC XY: 383AN XY: 724352
GnomAD4 genome AF: 0.00670 AC: 1020AN: 152316Hom.: 10 Cov.: 32 AF XY: 0.00642 AC XY: 478AN XY: 74484
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Ile775Lys in exon 20 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 2.3% (103/4400) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs62001050). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Hermansky-Pudlak syndrome 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at