6-15522822-C-CTT

Position:

• chr6-15522822-C-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_032122.5(DTNBP1):​c.*151_*152dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000859 in 1,375,388 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: DTNBP1 NM_032122.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000895 (1095/1223002) while in subpopulation NFE AF= 0.00112 (1031/919442). AF 95% confidence interval is 0.00106. There are 1 homozygotes in gnomad4_exome. There are 549 alleles in male gnomad4_exome subpopulation. Median coverage is 16. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.*151_*152dupAA		3_prime_UTR_variant	10/10	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537	c.*151_*152dupAA		3_prime_UTR_variant	10/10	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.000571 AC: 87 AN: 152268 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.000955

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000895 AC: 1095 AN: 1223002 Hom.: 1 Cov.: 16 AF XY: 0.000891 AC XY: 549 AN XY: 616064

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000511

Gnomad4 ASJ exome AF: 0.0000437

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000147

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.000572

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152386 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74518

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000432 Hom.: 0

Bravo AF: 0.000703

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hermansky-Pudlak syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs555440397; hg19: chr6-15523053;