GeneBe

rs4932265

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005829.5(AP3S2):​c.273+8460A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,364 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.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 24)

Consequence

AP3S2
NM_005829.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.643

Publications

16 publications found
Variant links:
Genes affected
AP3S2 (HGNC:571): (adaptor related protein complex 3 subunit sigma 2) Predicted to be involved in anterograde synaptic vesicle transport and vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of AP-3 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]
ARPIN-AP3S2 (HGNC:38824): (ARPIN-AP3S2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C15orf38 (chromosome 15 open reading frame 38) and AP3S2 (adaptor-related protein complex 3, sigma 2 subunit) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

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ACMG classification

Classification was made for transcript

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

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005829.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AP3S2
NM_005829.5
MANE Select
c.273+8460A>T
intron
N/ANP_005820.1
ARPIN-AP3S2
NM_001199058.2
c.876+8460A>T
intron
N/ANP_001185987.1
AP3S2
NR_023361.2
n.319-2637A>T
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AP3S2
ENST00000336418.9
TSL:1 MANE Select
c.273+8460A>T
intron
N/AENSP00000338777.4
ARPIN-AP3S2
ENST00000398333.7
TSL:2
c.876+8460A>T
intron
N/AENSP00000381377.3
AP3S2
ENST00000558806.5
TSL:1
n.*158+8460A>T
intron
N/AENSP00000454027.1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
150246
Hom.:
0
Cov.:
24
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000665
AC:
1
AN:
150364
Hom.:
0
Cov.:
24
AF XY:
0.0000136
AC XY:
1
AN XY:
73412
show subpopulations
African (AFR)
AF:
0.0000244
AC:
1
AN:
40962
American (AMR)
AF:
0.00
AC:
0
AN:
15092
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5040
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4726
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10176
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67620
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Alfa
AF:
0.00
Hom.:
5831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.90
DANN
Benign
0.47
PhyloP100
-0.64

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

Other links and lift over

dbSNP: rs4932265; hg19: chr15-90423293; API