chr15-89888534-A-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005829.5(AP3S2):āc.260T>Cā(p.Leu87Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
AP3S2
NM_005829.5 missense
NM_005829.5 missense
Scores
12
4
2
Clinical Significance
Conservation
PhyloP100: 9.24
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.953
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP3S2 | NM_005829.5 | c.260T>C | p.Leu87Ser | missense_variant | 3/6 | ENST00000336418.9 | |
ARPIN-AP3S2 | NM_001199058.2 | c.863T>C | p.Leu288Ser | missense_variant | 7/10 | ||
AP3S2 | NR_023361.2 | n.305T>C | non_coding_transcript_exon_variant | 3/7 | |||
AP3S2 | NR_037582.2 | n.301T>C | non_coding_transcript_exon_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP3S2 | ENST00000336418.9 | c.260T>C | p.Leu87Ser | missense_variant | 3/6 | 1 | NM_005829.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152252Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251390Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135890
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461854Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 727218
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.260T>C (p.L87S) alteration is located in exon 3 (coding exon 3) of the AP3S2 gene. This alteration results from a T to C substitution at nucleotide position 260, causing the leucine (L) at amino acid position 87 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.
MutationTaster
Benign
D;D;N;N
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
D;.;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0054);Gain of disorder (P = 0.0054);Gain of disorder (P = 0.0054);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at