rs754944359
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001128126.3(AP4S1):c.43C>G(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Consequence
AP4S1
NM_001128126.3 missense
NM_001128126.3 missense
Scores
10
7
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.82
Genes affected
AP4S1 (HGNC:575): (adaptor related protein complex 4 subunit sigma 1) This gene encodes a member of the adaptor complexes small subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.924
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
GnomAD3 exomes
AF:
AC:
1
AN:
251384
Hom.:
AF XY:
AC XY:
0
AN XY:
135872
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad SAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D;D;.;D;.;.;D;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;.;D;D;D;.;D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;H;H;H;.;H;H;.;H;H
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D
Polyphen
0.99, 1.0
.;D;D;.;.;D;.;.;.;D
Vest4
0.91, 0.93, 0.91, 0.92, 0.93, 0.91
MutPred
Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);
MVP
MPC
0.65
ClinPred
D
GERP RS
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