Variant 6-8064353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_201280.3(BLOC1S5):c.24C>T(p.Thr8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,611,786 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 11 hom. )

Consequence

BLOC1S5
NM_201280.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.643

Variant links:

Genes affected

BLOC1S5 (HGNC:18561): (biogenesis of lysosomal organelles complex 1 subunit 5) This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene. [provided by RefSeq, Dec 2010]

BLOC1S5 links:

BLOC1S5-TXNDC5 (HGNC:):

BLOC1S5-TXNDC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 6-8064353-G-A is Benign according to our data. Variant chr6-8064353-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656218.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.643 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BLOC1S5	NM_201280.3 linkuse as main transcript	c.24C>T	p.Thr8=	synonymous_variant	1/5	ENST00000397457.7
BLOC1S5-TXNDC5	NR_037616.1 linkuse as main transcript	n.62C>T		non_coding_transcript_exon_variant	1/13
EEF1E1-BLOC1S5	NR_037618.1 linkuse as main transcript	n.459-1737C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLOC1S5	ENST00000397457.7 linkuse as main transcript	c.24C>T	p.Thr8=	synonymous_variant	1/5	1	NM_201280.3	P1	Q8TDH9-1
BLOC1S5	ENST00000244777.6 linkuse as main transcript	c.24C>T	p.Thr8=	synonymous_variant, NMD_transcript_variant	1/6	1
BLOC1S5	ENST00000627748.2 linkuse as main transcript	c.24C>T	p.Thr8=	synonymous_variant, NMD_transcript_variant	1/6	1
BLOC1S5	ENST00000543936.7 linkuse as main transcript	c.24C>T	p.Thr8=	synonymous_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00342

AC:

842

AN:

246098

Hom.:

AF XY:

0.00329

AC XY:

441

AN XY:

133876

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00530

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00295

Gnomad FIN exome

AF:

0.00135

Gnomad NFE exome

AF:

0.00450

Gnomad OTH exome

AF:

0.00551

GnomAD4 exome

AF:

0.00395

AC:

5766

AN:

1459452

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2899

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.00509

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00297

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00440

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152334

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00466

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.00298

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00551

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

BLOC1S5: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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