chr6-8062574-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_201280.3(BLOC1S5):c.154del(p.Val52LeufsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
BLOC1S5
NM_201280.3 frameshift
NM_201280.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.69
Genes affected
BLOC1S5 (HGNC:18561): (biogenesis of lysosomal organelles complex 1 subunit 5) This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 6-8062574-AC-A is Pathogenic according to our data. Variant chr6-8062574-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3236053.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLOC1S5 | NM_201280.3 | c.154del | p.Val52LeufsTer10 | frameshift_variant | 2/5 | ENST00000397457.7 | |
BLOC1S5-TXNDC5 | NR_037616.1 | n.192del | non_coding_transcript_exon_variant | 2/13 | |||
EEF1E1-BLOC1S5 | NR_037618.1 | n.500del | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLOC1S5 | ENST00000397457.7 | c.154del | p.Val52LeufsTer10 | frameshift_variant | 2/5 | 1 | NM_201280.3 | P1 | |
BLOC1S5 | ENST00000244777.6 | c.154del | p.Val52LeufsTer10 | frameshift_variant, NMD_transcript_variant | 2/6 | 1 | |||
BLOC1S5 | ENST00000627748.2 | c.154del | p.Val52LeufsTer10 | frameshift_variant, NMD_transcript_variant | 2/6 | 1 | |||
BLOC1S5 | ENST00000543936.7 | c.154del | p.Val52LeufsTer10 | frameshift_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hermansky-Pudlak syndrome 11 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | MVZ Medizinische Genetik Mainz | Apr 28, 2022 | ACMG Criteria: PVS1_STR, PM2_SUP, PM3_SUP, PP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
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
No publications associated with this variant yet.