19-2140035-G-T

Position:

• chr19-2140035-G-T

Variant summary

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

The NM_001261826.3(AP3D1):​c.97-1321C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 152,164 control chromosomes in the GnomAD database, including 188 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 0.038 (188 hom., cov: 31)
• Consequence: AP3D1 NM_001261826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

Genes affected

AP3D1 (HGNC:568): (adaptor related protein complex 3 subunit delta 1) The protein encoded by this gene is a subunit of the AP3 adaptor-like complex, which is not clathrin-associated, but is associated with the golgi region, as well as more peripheral structures. The AP-3 complex facilitates the budding of vesicles from the golgi membrane, and may be directly involved in trafficking to lysosomes. This subunit is implicated in intracellular biogenesis and trafficking of pigment granules, and possibly platelet dense granules and neurotransmitter vesicles. Defects in this gene are a cause of a new type of Hermansky-Pudlak syndrome. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3D1	NM_001261826.3	c.97-1321C>A		intron_variant		ENST00000643116.3	NP_001248755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3D1	ENST00000643116.3	c.97-1321C>A		intron_variant			NM_001261826.3	ENSP00000495274.2

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5794 AN: 152046 Hom.: 188 Cov.: 31

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0350

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

GnomAD4 genome AF: 0.0381 AC: 5793 AN: 152164 Hom.: 188 Cov.: 31 AF XY: 0.0412 AC XY: 3068 AN XY: 74382

Gnomad4 AFR AF: 0.00930

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0358 Hom.: 19

Bravo AF: 0.0348

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.82
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: rs2238600; hg19: chr19-2140034;