rs771492578

Variant names:

• chr12-55719547-C-G
• rs771492578
• NM_001487.4:c.400C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-55719547-C-G
• chr12-55719547-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001487.4(BLOC1S1):​c.400C>G​(p.Arg134Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R134C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLOC1S1 NM_001487.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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]

ENSG00000258311 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S1	NM_001487.4	c.400C>G	p.Arg134Gly	missense_variant	Exon 4 of 4	ENST00000548925.6	NP_001478.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S1	ENST00000548925.6	c.400C>G	p.Arg134Gly	missense_variant	Exon 4 of 4	1	NM_001487.4	ENSP00000447537.1
ENSG00000258311	ENST00000550412.5	c.351+324C>G		intron_variant	Intron 3 of 3	2		ENSP00000447650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.024	D;T;T
Sift4G	Uncertain	0.037	D;T;T
Polyphen		0.98	D;.;.
Vest4		0.82
MVP		0.48
MPC		0.17
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.61
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs771492578; hg19: chr12-56113331;