rs3803915

Positions:

• chr19-2160530-C-A
• chr19-2160530-C-T

Variant summary

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

The ENST00000643010.1(AP3D1):​c.-103+3826G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,328 control chromosomes in the GnomAD database, including 1,397 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 0.13 (1397 hom., cov: 30)
• Consequence: AP3D1 ENST00000643010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3D1	XM_047439597.1	c.-103+3826G>T		intron_variant			XP_047295553.1
AP3D1	XM_047439598.1	c.-103+3826G>T		intron_variant			XP_047295554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3D1	ENST00000643010.1	c.-103+3826G>T		intron_variant				ENSP00000494100.1
AP3D1	ENST00000591284.2	n.-103+3826G>T		intron_variant		5		ENSP00000493531.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19698 AN: 151212 Hom.: 1398 Cov.: 30

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.130 AC: 19697 AN: 151328 Hom.: 1397 Cov.: 30 AF XY: 0.135 AC XY: 9969 AN XY: 73956

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.121

Alfa AF: 0.117 Hom.: 1843

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.45
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3803915; hg19: chr19-2160529;