NM_212550.5:c.144C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_212550.5(BLOC1S3):c.144C>A(p.Arg48Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,525,754 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.016 ( 216 hom. )

Consequence

BLOC1S3
NM_212550.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.333

Variant links:

Genes affected

BLOC1S3 (HGNC:20914): (biogenesis of lysosomal organelles complex 1 subunit 3) This gene encodes a protein that is a component of the BLOC1 multi-subunit protein complex. This complex is necessary for the biogenesis of specialized organelles of the endosomal-lysosomal system, including platelet dense granules and melanosomes. Mutations in this gene cause Hermansky-Pudlak syndrome 8, a disease characterized by lysosomal storage defects, bleeding due to platelet storage pool deficiency, and oculocutaneous albinism. [provided by RefSeq, Jul 2008]

BLOC1S3 links:

MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MARK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 19-45179440-C-A is Benign according to our data. Variant chr19-45179440-C-A is described in ClinVar as [Benign]. Clinvar id is 226463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.333 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1572/152300) while in subpopulation NFE AF= 0.0177 (1205/68006). AF 95% confidence interval is 0.0169. There are 16 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S3	NM_212550.5 link	c.144C>A	p.Arg48Arg	synonymous_variant	Exon 2 of 2	ENST00000433642.3	NP_997715.1	Q6QNY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLOC1S3	ENST00000433642.3 link	c.144C>A	p.Arg48Arg	synonymous_variant	Exon 2 of 2	2	NM_212550.5	ENSP00000393840.1	Q6QNY0
BLOC1S3	ENST00000587722.1 link	c.144C>A	p.Arg48Arg	synonymous_variant	Exon 1 of 1	6		ENSP00000468281.1	Q6QNY0
MARK4	ENST00000587566.5 link	c.-276-79549C>A		intron_variant	Intron 1 of 6	5		ENSP00000465414.1	K7EK17
BLOC1S3	ENST00000592910.1 link	c.-229C>A		upstream_gene_variant		2		ENSP00000466798.1	K7EN58

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1572

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0111

AC:

1445

AN:

129900

Hom.:

AF XY:

0.0109

AC XY:

787

AN XY:

72058

show subpopulations

Gnomad AFR exome

AF:

0.00333

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.00499

Gnomad EAS exome

AF:

0.000200

Gnomad SAS exome

AF:

0.00890

Gnomad FIN exome

AF:

0.00922

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.00931

GnomAD4 exome

AF:

0.0162

AC:

22245

AN:

1373454

Hom.:

216

Cov.:

AF XY:

0.0160

AC XY:

10839

AN XY:

677560

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00401

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.000114

Gnomad4 SAS exome

AF:

0.00967

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0103

AC:

1572

AN:

152300

Hom.:

Cov.:

AF XY:

0.00964

AC XY:

718

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00891

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0177

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00941

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg48Arg in exon 2 of BLOC1S3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 1.4% (108/7706) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs182286598). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over