GeneBe

5-78228244-TA-TAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003664.5(AP3B1):​c.280-8_280-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,552 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

AP3B1
NM_003664.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

0 publications found
Variant links:
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]
AP3B1 Gene-Disease associations (from GenCC):
  • Hermansky-Pudlak syndrome 2
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AP3B1NM_003664.5 linkc.280-8_280-6dupTTT splice_region_variant, intron_variant Intron 3 of 26 ENST00000255194.11 NP_003655.3
AP3B1NM_001271769.2 linkc.133-8_133-6dupTTT splice_region_variant, intron_variant Intron 3 of 26 NP_001258698.1
AP3B1NM_001410752.1 linkc.280-8_280-6dupTTT splice_region_variant, intron_variant Intron 3 of 22 NP_001397681.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AP3B1ENST00000255194.11 linkc.280-6_280-5insTTT splice_region_variant, intron_variant Intron 3 of 26 1 NM_003664.5 ENSP00000255194.7

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408552
Hom.:
0
Cov.:
26
AF XY:
0.00000142
AC XY:
1
AN XY:
701826
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31994
American (AMR)
AF:
0.00
AC:
0
AN:
43232
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25084
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38404
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83208
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5614
European-Non Finnish (NFE)
AF:
9.31e-7
AC:
1
AN:
1074064
Other (OTH)
AF:
0.00
AC:
0
AN:
58338
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs5868908; hg19: chr5-77524068; API