rs75792246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_212550.5(BLOC1S3):c.322C>G(p.Leu108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,475,054 control chromosomes in the GnomAD database, including 1,432 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 102 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1330 hom. )

Consequence

BLOC1S3
NM_212550.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.20

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008262664).

BP6

Variant 19-45179618-C-G is Benign according to our data. Variant chr19-45179618-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 179946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0291 (4425/152234) while in subpopulation NFE AF= 0.044 (2988/67978). AF 95% confidence interval is 0.0426. There are 102 homozygotes in gnomad4. There are 2131 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S3	NM_212550.5 link	c.322C>G	p.Leu108Val	missense_variant	Exon 2 of 2	ENST00000433642.3	NP_997715.1	Q6QNY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S3	ENST00000433642.3 link	c.322C>G	p.Leu108Val	missense_variant	Exon 2 of 2	2	NM_212550.5	ENSP00000393840.1		Q6QNY0

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4425

AN:

152126

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00719

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0570

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0439

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.0255

AC:

2078

AN:

81378

Hom.:

AF XY:

0.0251

AC XY:

1168

AN XY:

46468

show subpopulations

Gnomad AFR exome

AF:

0.00951

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00937

Gnomad FIN exome

AF:

0.0479

Gnomad NFE exome

AF:

0.0414

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0420

AC:

55597

AN:

1322820

Hom.:

1330

Cov.:

AF XY:

0.0411

AC XY:

26805

AN XY:

651658

show subpopulations

Gnomad4 AFR exome

AF:

0.00619

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.0000341

Gnomad4 SAS exome

AF:

0.00936

Gnomad4 FIN exome

AF:

0.0472

Gnomad4 NFE exome

AF:

0.0478

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.0291

AC:

4425

AN:

152234

Hom.:

102

Cov.:

AF XY:

0.0286

AC XY:

2131

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00714

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0570

Gnomad4 NFE

AF:

0.0440

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0334

Hom.:

Bravo

AF:

0.0259

ExAC

AF:

0.00905

AC:

126

Asia WGS

AF:

0.00408

AC:

AN:

3448

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 16, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Leu108Val in exon 2 of BLOC1S3: This variant is not expected to have clinical significance because it has been identified in 1.63% (35/2144) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNPrs75792246). -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 20, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 21, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

May 09, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;D

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.53

.;T

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.9

L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.18

T;T

Polyphen

1.0

D;D

Vest4

0.31

MPC

2.0

ClinPred

0.029

GERP RS

3.7

Varity_R

0.53

gMVP

0.31

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