NM_032122.5:c.511+3202T>C

Variant names:

• chr6-15589857-A-G
• rs9296986
• NM_032122.5:c.511+3202T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.511+3202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,174 control chromosomes in the GnomAD database, including 51,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51350 hom., cov: 31)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+3202T>C		intron_variant	Intron 7 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+3202T>C		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124562 AN: 152056 Hom.: 51303 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124664 AN: 152174 Hom.: 51350 Cov.: 31 AF XY: 0.826 AC XY: 61471 AN XY: 74398

African (AFR) AF: 0.864 AC: 35881 AN: 41514

American (AMR) AF: 0.838 AC: 12822 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2657 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5169 AN: 5178

South Asian (SAS) AF: 0.907 AC: 4366 AN: 4814

European-Finnish (FIN) AF: 0.842 AC: 8925 AN: 10598

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52261 AN: 67988

Other (OTH) AF: 0.815 AC: 1719 AN: 2108

Alfa AF: 0.794 Hom.: 5913

Bravo AF: 0.818

Asia WGS AF: 0.950 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9296986; hg19: chr6-15590088;