Variant chr19-2102028-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001261826.3(AP3D1):c.*145C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 642,794 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 12 hom. )

Consequence

AP3D1
NM_001261826.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.596

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-2102028-G-A is Benign according to our data. Variant chr19-2102028-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3340975.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00543 (2663/490480) while in subpopulation MID AF= 0.0263 (52/1980). AF 95% confidence interval is 0.0206. There are 12 homozygotes in gnomad4_exome. There are 1442 alleles in male gnomad4_exome subpopulation. Median coverage is 6. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3D1	NM_001261826.3 linkuse as main transcript	c.*145C>T		3_prime_UTR_variant	32/32	ENST00000643116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3D1	ENST00000643116.3 linkuse as main transcript	c.*145C>T		3_prime_UTR_variant	32/32		NM_001261826.3	P2	O14617-5

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1161

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00543

AC:

2663

AN:

490480

Hom.:

Cov.:

AF XY:

0.00550

AC XY:

1442

AN XY:

261998

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.00641

Gnomad4 ASJ exome

AF:

0.0102

Gnomad4 EAS exome

AF:

0.0000986

Gnomad4 SAS exome

AF:

0.00634

Gnomad4 FIN exome

AF:

0.00447

Gnomad4 NFE exome

AF:

0.00500

Gnomad4 OTH exome

AF:

0.00735

GnomAD4 genome

AF:

0.00763

AC:

1162

AN:

152314

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

597

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.00837

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.00448

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.00816

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over