17-42125841-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000346213.9(RAB5C):c.593G>A(p.Arg198Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,459,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
RAB5C
ENST00000346213.9 missense
ENST00000346213.9 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 6.06
Genes affected
RAB5C (HGNC:9785): (RAB5C, member RAS oncogene family) Members of the Rab protein family are small GTPases of the Ras superfamily that are thought to ensure fidelity in the process of docking and/or fusion of vesicles with their correct acceptor compartment (Han et al., 1996 [PubMed 8646882]).[supplied by OMIM, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16899791).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB5C | NM_004583.4 | c.593G>A | p.Arg198Gln | missense_variant | 6/6 | ENST00000346213.9 | NP_004574.2 | |
RAB5C | NM_001252039.2 | c.692G>A | p.Arg231Gln | missense_variant | 7/7 | NP_001238968.1 | ||
RAB5C | NM_201434.3 | c.593G>A | p.Arg198Gln | missense_variant | 7/7 | NP_958842.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAB5C | ENST00000346213.9 | c.593G>A | p.Arg198Gln | missense_variant | 6/6 | 1 | NM_004583.4 | ENSP00000345689.5 | ||
ENSG00000267261 | ENST00000592574.1 | c.441+2420G>A | intron_variant | 5 | ENSP00000468367.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246306Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 132994
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1459578Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 725742
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GnomAD4 genome Cov.: 31
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31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.593G>A (p.R198Q) alteration is located in exon 7 (coding exon 5) of the RAB5C gene. This alteration results from a G to A substitution at nucleotide position 593, causing the arginine (R) at amino acid position 198 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
Loss of methylation at R198 (P = 0.0707);Loss of methylation at R198 (P = 0.0707);.;
MVP
MPC
0.70
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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