rs758506

Positions:

chr19-45179566-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_212550.5(BLOC1S3):c.270G>A(p.Ala90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,515,430 control chromosomes in the GnomAD database, including 11,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1531 hom., cov: 33)

Exomes 𝑓: 0.12 ( 9722 hom. )

Consequence

BLOC1S3
NM_212550.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.815

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-45179566-G-A is Benign according to our data. Variant chr19-45179566-G-A is described in ClinVar as [Benign]. Clinvar id is 162790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.815 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLOC1S3	NM_212550.5 linkuse as main transcript	c.270G>A	p.Ala90=	synonymous_variant	2/2	ENST00000433642.3	NP_997715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BLOC1S3	ENST00000433642.3 linkuse as main transcript	c.270G>A	p.Ala90=	synonymous_variant	2/2	2	NM_212550.5	ENSP00000393840	P1
BLOC1S3	ENST00000587722.1 linkuse as main transcript	c.270G>A	p.Ala90=	synonymous_variant	1/1			ENSP00000468281	P1
MARK4	ENST00000587566.5 linkuse as main transcript	c.-276-79423G>A		intron_variant		5		ENSP00000465414

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20220

AN:

152088

Hom.:

1528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0540

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.114

AC:

12606

AN:

110724

Hom.:

867

AF XY:

0.118

AC XY:

7229

AN XY:

61382

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.0586

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.115

AC:

157440

AN:

1363234

Hom.:

9722

Cov.:

AF XY:

0.116

AC XY:

77948

AN XY:

672140

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0631

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0682

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.133

AC:

20230

AN:

152196

Hom.:

1531

Cov.:

AF XY:

0.131

AC XY:

9772

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0878

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.0664

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.123

Hom.:

228

Bravo

AF:

0.138

Asia WGS

AF:

0.178

AC:

616

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ala90Ala 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 12.6% (211/1680) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs758506). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 11, 2016	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Hermansky-Pudlak syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.4

DANN

Benign

0.84

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