Genetic Variant AP3B2:p.Ile1096Thr (chr15-82659579-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001278512.2(AP3B2):c.3287T>C(p.Ile1096Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

AP3B2
NM_001278512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Publications

0 publications found

Variant links:

Genes affected

AP3B2 (HGNC:567): (adaptor related protein complex 3 subunit beta 2) Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]

AP3B2 links:

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

CPEB1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22985926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3B2	NM_001278512.2	MANE Select	c.3287T>C	p.Ile1096Thr	missense	Exon 27 of 27	NP_001265441.1	Q13367-4
AP3B2	NM_004644.5		c.3230T>C	p.Ile1077Thr	missense	Exon 26 of 26	NP_004635.2
AP3B2	NM_001278511.2		c.3134T>C	p.Ile1045Thr	missense	Exon 25 of 25	NP_001265440.1	Q13367-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3B2	ENST00000535359.6	TSL:1 MANE Select	c.3287T>C	p.Ile1096Thr	missense	Exon 27 of 27	ENSP00000440984.1	Q13367-4
AP3B2	ENST00000261722.8	TSL:1	c.3248T>C	p.Ile1083Thr	missense	Exon 26 of 26	ENSP00000261722.4	A0A5F9UJV3
AP3B2	ENST00000535348.5	TSL:1	c.3134T>C	p.Ile1045Thr	missense	Exon 25 of 25	ENSP00000438721.1	Q13367-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249192

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111858

Other (OTH)

AF:

0.0000166

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.089

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Benign

0.052

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

PhyloP100

5.9

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.030

REVEL

Benign

0.15

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.11

MutPred

0.55

Gain of disorder (P = 0.0216)

MVP

0.15

MPC

0.068

ClinPred

0.58

GERP RS

2.7

Varity_R

0.031

gMVP

0.11

Mutation Taster

=84/16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over