rs369022314
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201280.3(BLOC1S5):c.373G>C(p.Glu125Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000484 in 1,610,732 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 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
BLOC1S5
NM_201280.3 missense
NM_201280.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 4.66
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]
EEF1E1-BLOC1S5 (HGNC:49187): (EEF1E1-BLOC1S5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) and MUTED (muted homolog) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]
BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16555253).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| BLOC1S5 | ENST00000397457.7 | c.373G>C | p.Glu125Gln | missense_variant | Exon 4 of 5 | 1 | NM_201280.3 | ENSP00000380598.2 | ||
| EEF1E1-BLOC1S5 | ENST00000397456.2 | n.*189G>C | non_coding_transcript_exon_variant | Exon 6 of 7 | 3 | ENSP00000380597.2 | ||||
| BLOC1S5-TXNDC5 | ENST00000439343.2 | n.361G>C | non_coding_transcript_exon_variant | Exon 4 of 13 | 2 | ENSP00000454697.1 | ||||
| EEF1E1-BLOC1S5 | ENST00000397456.2 | n.*189G>C | 3_prime_UTR_variant | Exon 6 of 7 | 3 | ENSP00000380597.2 |
Frequencies
GnomAD3 genomes 0.000250 AC: 38AN: 151964Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000679 AC: 17AN: 250276Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135308
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1458650Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 725792
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GnomAD4 genome 0.000250 AC: 38AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Sep 14, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.373G>C (p.E125Q) alteration is located in exon 4 (coding exon 4) of the BLOC1S5 gene. This alteration results from a G to C substitution at nucleotide position 373, causing the glutamic acid (E) at amino acid position 125 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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