5-78002314-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000519295.6(AP3B1):c.*588A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 297,896 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (112 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (18 hom.)
• Consequence: AP3B1 ENST00000519295.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.698

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 5-78002314-T-C is Benign according to our data. Variant chr5-78002314-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B1	NM_001271769.2	c.*588A>G		3_prime_UTR_variant	27/27
AP3B1	NM_003664.5			downstream_gene_variant		ENST00000255194.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11			downstream_gene_variant		1	NM_003664.5	P2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3398 AN: 152160 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0687

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00523 AC: 761 AN: 145618 Hom.: 18 Cov.: 0 AF XY: 0.00487 AC XY: 361 AN XY: 74104

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.0177

Gnomad4 ASJ exome AF: 0.00200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000107

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.0224 AC: 3404 AN: 152278 Hom.: 112 Cov.: 33 AF XY: 0.0212 AC XY: 1581 AN XY: 74462

Gnomad4 AFR AF: 0.0686

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0125 Hom.: 3

Bravo AF: 0.0257

Asia WGS AF: 0.00607 AC: 21 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hermansky-Pudlak syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	11
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs114954951; hg19: chr5-77298138;