dbSNP rs779511911: AP3B1:p.Ser527Ile (chr5-78141213-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003664.5(AP3B1):c.1580G>T(p.Ser527Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S527N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AP3B1
NM_003664.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.298

Publications

1 publications found

Variant links:

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

AP3B1 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

AP3B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18569812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003664.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AP3B1	NM_003664.5	MANE Select	c.1580G>T	p.Ser527Ile	missense	Exon 15 of 27	NP_003655.3
AP3B1	NM_001271769.2		c.1433G>T	p.Ser478Ile	missense	Exon 15 of 27	NP_001258698.1
AP3B1	NM_001410752.1		c.1580G>T	p.Ser527Ile	missense	Exon 15 of 23	NP_001397681.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AP3B1	ENST00000255194.11	TSL:1 MANE Select	c.1580G>T	p.Ser527Ile	missense	Exon 15 of 27	ENSP00000255194.7
AP3B1	ENST00000519295.7	TSL:1	c.1433G>T	p.Ser478Ile	missense	Exon 15 of 27	ENSP00000430597.1
AP3B1	ENST00000695515.1		c.1580G>T	p.Ser527Ile	missense	Exon 15 of 26	ENSP00000511978.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251228

AF XY:

0.00000736

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111776

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000371

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Benign

0.073

Eigen_PC

Benign

0.0056

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.30

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.087

Sift

Benign

0.051

Sift4G

Benign

0.081

Polyphen

0.91

Vest4

0.35

MVP

0.34

MPC

0.18

ClinPred

0.90

GERP RS

3.1

Varity_R

0.14

gMVP

0.48

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over