6-15593088-GAAAAA-GAA

Variant names:

• chr6-15593088-GAAA-G
• rs199770715
• NM_032122.5:c.489-10_489-8delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_032122.5(DTNBP1):​c.489-10_489-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,338,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: DTNBP1 NM_032122.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000512 (616/1202396) while in subpopulation AMR AF= 0.00199 (57/28586). AF 95% confidence interval is 0.00158. There are 0 homozygotes in gnomad4_exome. There are 310 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000147 AC: 2 AN: 135856 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000736

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000512 AC: 616 AN: 1202396 Hom.: 0 AF XY: 0.000518 AC XY: 310 AN XY: 599006

Gnomad4 AFR exome AF: 0.000870

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.000732

Gnomad4 EAS exome AF: 0.000995

Gnomad4 SAS exome AF: 0.000863

Gnomad4 FIN exome AF: 0.000923

Gnomad4 NFE exome AF: 0.000396

Gnomad4 OTH exome AF: 0.000379

GnomAD4 genome AF: 0.0000147 AC: 2 AN: 135856 Hom.: 0 Cov.: 28 AF XY: 0.0000153 AC XY: 1 AN XY: 65464

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000736

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000136

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs199770715; hg19: chr6-15593319;