Variant 6-15593088-GAAAAA-GAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_032122.5(DTNBP1):c.489-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 28)

Exomes 𝑓: 0.13 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DTNBP1
NM_032122.5 splice_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2B:2

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

DTNBP1 (HGNC:17328): (dystrobrevin binding protein 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.489-8delT		splice_region_variant, intron_variant		ENST00000344537.10	NP_115498.2	Q96EV8-1A0A0S2Z5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 link	c.489-8delT		splice_region_variant, intron_variant		1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

295

AN:

135690

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000823

Gnomad SAS

AF:

0.000463

Gnomad FIN

AF:

0.00410

Gnomad MID

AF:

0.00340

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00269

GnomAD4 exome

AF:

0.134

AC:

135198

AN:

1010718

Hom.:

Cov.:

AF XY:

0.135

AC XY:

67908

AN XY:

502030

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00219

AC:

297

AN:

135722

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

138

AN XY:

65422

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00103

Gnomad4 SAS

AF:

0.000465

Gnomad4 FIN

AF:

0.00410

Gnomad4 NFE

AF:

0.00136

Gnomad4 OTH

AF:

0.00267

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Hermansky-Pudlak syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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