rs2385821

Variant names:

• chr19-2120155-A-G
• rs2385821
• NM_001261826.3:c.1481+707T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

AP3D1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 10

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AP3D1	NM_001261826.3	c.1481+707T>C		intron_variant	Intron 14 of 31	ENST00000643116.3	NP_001248755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3D1	ENST00000643116.3	c.1481+707T>C		intron_variant	Intron 14 of 31		NM_001261826.3	ENSP00000495274.2

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

African (AFR) AF: 0.991 AC: 41158 AN: 41532

American (AMR) AF: 0.919 AC: 14037 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 3428 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5164

South Asian (SAS) AF: 0.960 AC: 4630 AN: 4822

European-Finnish (FIN) AF: 0.989 AC: 10494 AN: 10606

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.960 AC: 65294 AN: 68002

Other (OTH) AF: 0.963 AC: 2035 AN: 2114

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
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2385821; hg19: chr19-2120154;