5-115842054-T-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001284.4(AP3S1):āc.17T>Cā(p.Leu6Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 35)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AP3S1
NM_001284.4 missense
NM_001284.4 missense
Scores
14
3
2
Clinical Significance
Conservation
PhyloP100: 5.10
Genes affected
AP3S1 (HGNC:2013): (adaptor related protein complex 3 subunit sigma 1) This gene encodes a subunit of the AP3 adaptor complex. This complex functions in the formation of subcellular vesicles budded from the Golgi body. Several related pseudogenes of this gene have been found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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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, 0.986
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP3S1 | NM_001284.4 | c.17T>C | p.Leu6Pro | missense_variant | 1/6 | ENST00000316788.12 | NP_001275.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP3S1 | ENST00000316788.12 | c.17T>C | p.Leu6Pro | missense_variant | 1/6 | 1 | NM_001284.4 | ENSP00000325369.7 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 genomes
Cov.:
35
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1440188Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0AN XY: 714836
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1440188
Hom.:
Cov.:
61
AF XY:
AC XY:
0
AN XY:
714836
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 35
GnomAD4 genome
Cov.:
35
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 | Feb 14, 2023 | The c.17T>C (p.L6P) alteration is located in exon 1 (coding exon 1) of the AP3S1 gene. This alteration results from a T to C substitution at nucleotide position 17, causing the leucine (L) at amino acid position 6 to be replaced by a proline (P). 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;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Gain of disorder (P = 0.0176);Gain of disorder (P = 0.0176);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.