Genetic Variant DTNBP1:c.489-10_489-8dupTTT (chr6-15593088-G-GAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_032122.5(DTNBP1):c.489-10_489-8dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DTNBP1
NM_032122.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

DTNBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5 link	c.489-10_489-8dupTTT		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000344537.10	NP_115498.2	Q96EV8-1A0A0S2Z5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10 link	c.489-8_489-7insTTT		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_032122.5	ENSP00000341680.6		Q96EV8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

135858

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000468

AC:

AN:

98290

AF XY:

0.000431

show subpopulations

Gnomad AFR exome

AF:

0.000754

Gnomad AMR exome

AF:

0.000854

Gnomad ASJ exome

AF:

0.000642

Gnomad EAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

148

AN:

1210518

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

603036

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000263

AC:

AN:

26610

American (AMR)

AF:

0.000381

AC:

AN:

28908

Ashkenazi Jewish (ASJ)

AF:

0.000182

AC:

AN:

21992

East Asian (EAS)

AF:

0.000339

AC:

AN:

35360

South Asian (SAS)

AF:

0.000334

AC:

AN:

68836

European-Finnish (FIN)

AF:

0.0000217

AC:

AN:

46038

Middle Eastern (MID)

AF:

0.000414

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.0000884

AC:

AN:

927420

Other (OTH)

AF:

0.000119

AC:

AN:

50528

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.271

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

135858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65466

African (AFR)

AF:

0.00

AC:

AN:

37424

American (AMR)

AF:

0.00

AC:

AN:

13580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3238

East Asian (EAS)

AF:

0.00

AC:

AN:

4858

South Asian (SAS)

AF:

0.00

AC:

AN:

4318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62090

Other (OTH)

AF:

0.00

AC:

AN:

1862

Alfa

AF:

0.000301

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over