NM_001487.4:c.4G>A

Variant summary

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

The NM_001487.4(BLOC1S1):​c.4G>A​(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

BLOC1S1
NM_001487.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.472
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]
ITGA7 (HGNC:6143): (integrin subunit alpha 7) The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

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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=0.07506344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BLOC1S1NM_001487.4 linkc.4G>A p.Ala2Thr missense_variant Exon 1 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.4G>A p.Ala2Thr missense_variant Exon 1 of 4 1 NM_001487.4 ENSP00000447537.1 P78537-1
ENSG00000258311ENST00000550412.5 linkc.4G>A p.Ala2Thr missense_variant Exon 1 of 4 2 ENSP00000447650.1 F8W036

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.12e-7
AC:
1
AN:
1403856
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
693686
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:
9.23e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
10
DANN
Benign
0.89
DEOGEN2
Benign
0.055
.;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.077
N
LIST_S2
Benign
0.50
T;T;T
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.075
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.17
N;N;N
REVEL
Benign
0.023
Sift
Uncertain
0.029
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.013
B;.;B
Vest4
0.17
MutPred
0.24
Gain of catalytic residue at P3 (P = 0.005);Gain of catalytic residue at P3 (P = 0.005);Gain of catalytic residue at P3 (P = 0.005);
MVP
0.081
MPC
0.022
ClinPred
0.15
T
GERP RS
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.051
gMVP
0.077

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs933348517; hg19: chr12-56109839; API