15-50908899-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_007347.5(AP4E1):c.121C>A(p.Arg41Ser) 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 (★).
Frequency
Genomes: not found (cov: 34)
Consequence
AP4E1
NM_007347.5 missense
NM_007347.5 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 4.08
Publications
0 publications found
Genes affected
AP4E1 (HGNC:573): (adaptor related protein complex 4 subunit epsilon 1) This gene encodes a member of the adaptor complexes large 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 a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
AP4E1 Gene-Disease associations (from GenCC):
- AP-4 deficiency syndromeInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hereditary spastic paraplegia 51Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- AP4-related intellectual disability and spastic paraplegiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.835
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_007347.5. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AP4E1 | TSL:1 MANE Select | c.121C>A | p.Arg41Ser | missense | Exon 1 of 21 | ENSP00000261842.5 | Q9UPM8-1 | ||
| AP4E1 | TSL:1 | c.-128C>A | 5_prime_UTR | Exon 1 of 21 | ENSP00000452976.1 | Q9UPM8-2 | |||
| AP4E1 | TSL:1 | n.121C>A | non_coding_transcript_exon | Exon 1 of 21 | ENSP00000452712.1 | H0YK95 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Spastic paraplegia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0122)
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
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