15-45587486-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000564080.1(ENSG00000260170):c.-57C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,585,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
ENSG00000260170
ENST00000564080.1 5_prime_UTR_premature_start_codon_gain
ENST00000564080.1 5_prime_UTR_premature_start_codon_gain
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.925
Genes affected
BLOC1S6 (HGNC:8549): (biogenesis of lysosomal organelles complex 1 subunit 6) The protein encoded by this gene may play a role in intracellular vesicle trafficking. It interacts with Syntaxin 13 which mediates intracellular membrane fusion. Mutations in this gene cause symptoms associated with Hermansky-Pudlak syndrome-9. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06358239).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BLOC1S6 | NM_012388.4 | c.43C>T | p.Arg15Trp | missense_variant | 1/5 | ENST00000220531.9 | NP_036520.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENSG00000260170 | ENST00000564080.1 | c.-57C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/6 | 3 | ENSP00000455047.1 | ||||
BLOC1S6 | ENST00000220531.9 | c.43C>T | p.Arg15Trp | missense_variant | 1/5 | 1 | NM_012388.4 | ENSP00000220531.4 | ||
ENSG00000260170 | ENST00000564080.1 | c.-57C>T | 5_prime_UTR_variant | 1/6 | 3 | ENSP00000455047.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000198 AC: 4AN: 202106Hom.: 0 AF XY: 0.0000184 AC XY: 2AN XY: 108908
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GnomAD4 exome AF: 0.00000419 AC: 6AN: 1433586Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2AN XY: 710588
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hermansky-Pudlak syndrome 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 05, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 15 of the BLOC1S6 protein (p.Arg15Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BLOC1S6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1027192). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;D;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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