rs2385821

Positions:

• chr19-2120155-A-G
• chr19-2120155-A-T

Variant summary

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

The NM_001261826.3(AP3D1):​c.1481+707T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,200 control chromosomes in the GnomAD database, including 71,400 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 0.97 (71400 hom., cov: 30)
• Consequence: AP3D1 NM_001261826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3D1	NM_001261826.3	c.1481+707T>C		intron_variant		ENST00000643116.3	NP_001248755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3D1	ENST00000643116.3	c.1481+707T>C		intron_variant			NM_001261826.3	ENSP00000495274	P2

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147249 AN: 152082 Hom.: 71346 Cov.: 30

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.968 AC: 147363 AN: 152200 Hom.: 71400 Cov.: 30 AF XY: 0.969 AC XY: 72104 AN XY: 74414

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.987

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.960

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.963

Alfa AF: 0.967 Hom.: 9678

Bravo AF: 0.962

Asia WGS AF: 0.983 AC: 3417 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	1.4
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2385821; hg19: chr19-2120154;