19-2102247-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001261826.3(AP3D1):c.3574G>A(p.Asp1192Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D1192D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

AP3D1
NM_001261826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.43

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 10
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

AP3D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35134372).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3D1	NM_001261826.3	MANE Select	c.3574G>A	p.Asp1192Asn	missense	Exon 32 of 32	NP_001248755.1	O14617-5
AP3D1	NM_001374799.1		c.3538G>A	p.Asp1180Asn	missense	Exon 32 of 32	NP_001361728.1	A0A8V8TQW4
AP3D1	NM_003938.8		c.3388G>A	p.Asp1130Asn	missense	Exon 30 of 30	NP_003929.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3D1	ENST00000643116.3	MANE Select	c.3574G>A	p.Asp1192Asn	missense	Exon 32 of 32	ENSP00000495274.2	O14617-5
AP3D1	ENST00000345016.9	TSL:1	c.3388G>A	p.Asp1130Asn	missense	Exon 30 of 30	ENSP00000344055.4	O14617-1
AP3D1	ENST00000591650.1	TSL:1	n.811G>A		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000403

AC:

AN:

248044

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111760

Other (OTH)

AF:

0.0000331

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41414

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.027

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.1

PhyloP100

5.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.4

REVEL

Uncertain

0.29

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.041

Polyphen

1.0

Vest4

0.60

MVP

0.64

MPC

0.33

ClinPred

0.32

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.58

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over