5-78002861-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_003664.5(AP3B1):c.*41A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0115 in 1,613,294 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (14 hom., cov: 32)
  • Exomes 𝑓: 0.012 (128 hom.)
• Consequence: AP3B1 NM_003664.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.85

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=-0.45).
• BP6: Variant 5-78002861-T-C is Benign according to our data. Variant chr5-78002861-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00886 (1349/152322) while in subpopulation NFE AF= 0.0126 (855/68038). AF 95% confidence interval is 0.0119. There are 14 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B1	NM_003664.5	c.*41A>G		3_prime_UTR_variant	27/27	ENST00000255194.11
AP3B1	NM_001271769.2	c.*41A>G		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11	c.*41A>G		3_prime_UTR_variant	27/27	1	NM_003664.5	P2

Frequencies

GnomAD3 genomes AF: 0.00886 AC: 1349 AN: 152204 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00905 AC: 2275 AN: 251436 Hom.: 19 AF XY: 0.00896 AC XY: 1217 AN XY: 135884

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00844

Gnomad ASJ exome AF: 0.0229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00444

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.0118 AC: 17248 AN: 1460972 Hom.: 128 Cov.: 31 AF XY: 0.0116 AC XY: 8449 AN XY: 726864

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00986

Gnomad4 ASJ exome AF: 0.0220

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00486

Gnomad4 FIN exome AF: 0.00586

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.00886 AC: 1349 AN: 152322 Hom.: 14 Cov.: 32 AF XY: 0.00834 AC XY: 621 AN XY: 74486

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.0105 Hom.: 4

Bravo AF: 0.00990

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	16
Dann	Benign	0.86

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: rs112214336; hg19: chr5-77298685; COSMIC: COSV54876708; COSMIC: COSV54876708;