19-2102511-C-G

Position:

• chr19-2102511-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001261826.3(AP3D1):​c.3553-243G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,746 control chromosomes in the GnomAD database, including 1,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1296 hom., cov: 32)
• Consequence: AP3D1 NM_001261826.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.609

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-2102511-C-G is Benign according to our data. Variant chr19-2102511-C-G is described in ClinVar as [Benign]. Clinvar id is 1221081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3D1	NM_001261826.3	c.3553-243G>C		intron_variant		ENST00000643116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3D1	ENST00000643116.3	c.3553-243G>C		intron_variant			NM_001261826.3	P2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18906 AN: 151628 Hom.: 1295 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0881

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.125 AC: 18912 AN: 151746 Hom.: 1296 Cov.: 32 AF XY: 0.124 AC XY: 9199 AN XY: 74138

Gnomad4 AFR AF: 0.0862

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0611 Hom.: 79

Bravo AF: 0.115

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.71

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: rs111856206; hg19: chr19-2102510;