Genetic Variant DTNBP1:c.489-12_489-8dupTTTTT (chr6-15593088-G-GAAAAA) – 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.489-12_489-8dupTTTTT 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: 0.0000017 ( 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

0 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), G2P, ClinGen

DTNBP1 links:

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ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	NM_032122.5	MANE Select	c.489-12_489-8dupTTTTT	splice_region intron	N/A	NP_115498.2
DTNBP1	NM_001271668.2		c.438-12_438-8dupTTTTT	splice_region intron	N/A	NP_001258597.1	A6NFV8
DTNBP1	NM_001271669.2		c.384-12_384-8dupTTTTT	splice_region intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.489-8_489-7insTTTTT	splice_region intron	N/A	ENSP00000341680.6	Q96EV8-1
DTNBP1	ENST00000622898.4	TSL:1	c.384-8_384-7insTTTTT	splice_region intron	N/A	ENSP00000481997.1	A0A087WYP9
DTNBP1	ENST00000338950.9	TSL:1	c.489-8_489-7insTTTTT	splice_region intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

135860

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

GnomAD4 exome

AF:

0.00000165

AC:

AN:

1211166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

603402

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

26632

American (AMR)

AF:

0.00

AC:

AN:

28930

Ashkenazi Jewish (ASJ)

AF:

0.0000455

AC:

AN:

21998

East Asian (EAS)

AF:

0.00

AC:

AN:

35388

South Asian (SAS)

AF:

0.00

AC:

AN:

68922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

927854

Other (OTH)

AF:

0.00

AC:

AN:

50572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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:

135860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65466

African (AFR)

AF:

0.00

AC:

AN:

37426

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:

7346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62092

Other (OTH)

AF:

0.00

AC:

AN:

1862

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over