5-78002795-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003664.5(AP3B1):c.*107T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,242,656 control chromosomes in the GnomAD database, including 41,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7471 hom., cov: 32)
  • Exomes 𝑓: 0.24 (33862 hom.)
• Consequence: AP3B1 NM_003664.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-78002795-A-T is Benign according to our data. Variant chr5-78002795-A-T is described in ClinVar as [Benign]. Clinvar id is 354217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B1	NM_003664.5	c.*107T>A		3_prime_UTR_variant	27/27	ENST00000255194.11
AP3B1	NM_001271769.2	c.*107T>A		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11	c.*107T>A		3_prime_UTR_variant	27/27	1	NM_003664.5	P2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44715 AN: 152002 Hom.: 7440 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.238 AC: 259595 AN: 1090536 Hom.: 33862 Cov.: 15 AF XY: 0.233 AC XY: 130487 AN XY: 559592

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.294 AC: 44796 AN: 152120 Hom.: 7471 Cov.: 32 AF XY: 0.292 AC XY: 21730 AN XY: 74366

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.303

Alfa AF: 0.253 Hom.: 676

Bravo AF: 0.321

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Hermansky-Pudlak syndrome Benign:1

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	-0.53
Cadd	Benign	9.1
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11552314; hg19: chr5-77298619; COSMIC: COSV54878566; COSMIC: COSV54878566;