12-55716951-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001487.4(BLOC1S1):​c.164C>T​(p.Ala55Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,844 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BLOC1S1
NM_001487.4 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70
Variant links:
Genes affected
BLOC1S1 (HGNC:4200): (biogenesis of lysosomal organelles complex 1 subunit 1) BLOC1S1 is a component of the ubiquitously expressed BLOC1 multisubunit protein complex. BLOC1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules (Starcevic and Dell'Angelica, 2004 [PubMed 15102850]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BLOC1S1NM_001487.4 linkc.164C>T p.Ala55Val missense_variant Exon 2 of 4 ENST00000548925.6 NP_001478.2 P78537-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BLOC1S1ENST00000548925.6 linkc.164C>T p.Ala55Val missense_variant Exon 2 of 4 1 NM_001487.4 ENSP00000447537.1 P78537-1
ENSG00000258311ENST00000550412.5 linkc.164C>T p.Ala55Val missense_variant Exon 2 of 4 2 ENSP00000447650.1 F8W036

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1440844
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
716452
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:
9.06e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.164C>T (p.A55V) alteration is located in exon 2 (coding exon 2) of the BLOC1S1 gene. This alteration results from a C to T substitution at nucleotide position 164, causing the alanine (A) at amino acid position 55 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
.;T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Pathogenic
0.89
D;D;D
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.6
.;M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.6
D;D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0030
D;D;D
Sift4G
Benign
0.081
T;D;T
Polyphen
0.98
D;P;D
Vest4
0.82
MutPred
0.79
Loss of disorder (P = 0.0705);Loss of disorder (P = 0.0705);Loss of disorder (P = 0.0705);
MVP
0.70
MPC
0.16
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.71
gMVP
0.69

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: chr12-56110735; API