chr9-125213414-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_005833.4(RABEPK):c.256C>T(p.Arg86Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
RABEPK
NM_005833.4 missense
NM_005833.4 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 3.26
Genes affected
RABEPK (HGNC:16896): (Rab9 effector protein with kelch motifs) Predicted to be involved in receptor-mediated endocytosis and vesicle docking involved in exocytosis. Predicted to be located in cytoplasmic vesicle; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.2836648).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RABEPK | NM_005833.4 | c.256C>T | p.Arg86Trp | missense_variant | Exon 4 of 8 | ENST00000373538.8 | NP_005824.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 251146Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135734
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461640Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727132
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74426
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
High myopia Uncertain:1
Dec 17, 2018
Institute of Human Genetics, Polish Academy of Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;T;T;T;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;H;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MVP
MPC
0.24
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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