rs2238600

Variant names:

• chr19-2140035-G-T
• rs2238600
• NM_001261826.3:c.97-1321C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261826.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3D1	NM_001261826.3	MANE Select	c.97-1321C>A		intron	N/A	NP_001248755.1	O14617-5
	AP3D1	NM_001374799.1		c.97-1321C>A		intron	N/A	NP_001361728.1	A0A8V8TQW4
	AP3D1	NM_003938.8		c.97-1321C>A		intron	N/A	NP_003929.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3D1	ENST00000643116.3	MANE Select	c.97-1321C>A		intron	N/A	ENSP00000495274.2	O14617-5
	AP3D1	ENST00000345016.9	TSL:1	c.97-1321C>A		intron	N/A	ENSP00000344055.4	O14617-1
	AP3D1	ENST00000920155.1		c.97-1321C>A		intron	N/A	ENSP00000590214.1

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

African (AFR) AF: 0.00930 AC: 386 AN: 41524

American (AMR) AF: 0.0373 AC: 570 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.140 AC: 721 AN: 5168

South Asian (SAS) AF: 0.0675 AC: 325 AN: 4818

European-Finnish (FIN) AF: 0.0883 AC: 936 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2702 AN: 67996

Other (OTH) AF: 0.0342 AC: 72 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.82
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238600; hg19: chr19-2140034;