6-8062559-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201280.3(BLOC1S5):​c.170C>G​(p.Thr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

BLOC1S5
NM_201280.3 missense

Scores

5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13
Variant links:
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=0.23813784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BLOC1S5NM_201280.3 linkc.170C>G p.Thr57Ser missense_variant Exon 2 of 5 ENST00000397457.7 NP_958437.1 Q8TDH9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BLOC1S5ENST00000397457.7 linkc.170C>G p.Thr57Ser missense_variant Exon 2 of 5 1 NM_201280.3 ENSP00000380598.2 Q8TDH9-1
EEF1E1-BLOC1S5ENST00000397456.2 linkn.442C>G non_coding_transcript_exon_variant Exon 4 of 7 3 ENSP00000380597.2 C9J1V9
BLOC1S5-TXNDC5ENST00000439343.2 linkn.158C>G non_coding_transcript_exon_variant Exon 2 of 13 2 ENSP00000454697.1 H3BN57

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000208
AC:
3
AN:
1444616
Hom.:
0
Cov.:
27
AF XY:
0.00000278
AC XY:
2
AN XY:
719216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
0.0063
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Uncertain
0.51
D;.
Eigen
Benign
-0.086
Eigen_PC
Benign
-0.062
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;.
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.15
Sift
Uncertain
0.026
D;.
Sift4G
Uncertain
0.057
T;T
Polyphen
0.47
P;.
Vest4
0.46
MutPred
0.30
Gain of phosphorylation at T57 (P = 0.061);Gain of phosphorylation at T57 (P = 0.061);
MVP
0.47
MPC
0.16
ClinPred
0.31
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.061
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-8062792; API