rs727502866
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_032122.5(DTNBP1):c.177G>A(p.Trp59*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000411 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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: 0.0000041 ( 0 hom. )
Consequence
DTNBP1
NM_032122.5 stop_gained
NM_032122.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.53
Genes affected
DTNBP1 (HGNC:17328): (dystrobrevin binding protein 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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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 6-15637789-C-T is Pathogenic according to our data. Variant chr6-15637789-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 162098.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNBP1 | NM_032122.5 | c.177G>A | p.Trp59* | stop_gained | 4/10 | ENST00000344537.10 | NP_115498.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNBP1 | ENST00000344537.10 | c.177G>A | p.Trp59* | stop_gained | 4/10 | 1 | NM_032122.5 | ENSP00000341680.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250858Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135630
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461234Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726956
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hermansky-Pudlak syndrome 7 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2013 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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