rs13163558

chr5-78281882-G-Achr5-78281882-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003664.5(AP3B1):c.128+12570C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,994 control chromosomes in the GnomAD database, including 4,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4412 hom., cov: 31)
• Consequence: AP3B1 NM_003664.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B1	NM_003664.5	c.128+12570C>T		intron_variant		ENST00000255194.11
AP3B1	NM_001271769.2	c.-20+12558C>T		intron_variant
AP3B1	NM_001410752.1	c.128+12570C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11	c.128+12570C>T		intron_variant		1	NM_003664.5	P2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33002 AN: 151876 Hom.: 4416 Cov.: 31

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 33000 AN: 151994 Hom.: 4412 Cov.: 31 AF XY: 0.217 AC XY: 16154 AN XY: 74278

Gnomad4 AFR AF: 0.0724

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.223

Alfa AF: 0.270 Hom.: 2790

Bravo AF: 0.198

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.85
Dann	Benign	0.70

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: rs13163558; hg19: chr5-77577706;