17-42125841-C-T

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

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
Variant links:
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]

Genome browser will be placed here

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
RAB5CNM_004583.4 linkuse as main transcriptc.593G>A p.Arg198Gln missense_variant 6/6 ENST00000346213.9 NP_004574.2 P51148-1A0A024R1U4
RAB5CNM_001252039.2 linkuse as main transcriptc.692G>A p.Arg231Gln missense_variant 7/7 NP_001238968.1 P51148-2
RAB5CNM_201434.3 linkuse as main transcriptc.593G>A p.Arg198Gln missense_variant 7/7 NP_958842.1 P51148-1A0A024R1U4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAB5CENST00000346213.9 linkuse as main transcriptc.593G>A p.Arg198Gln missense_variant 6/61 NM_004583.4 ENSP00000345689.5 P51148-1
ENSG00000267261ENST00000592574.1 linkuse as main transcriptc.441+2420G>A intron_variant 5 ENSP00000468367.1 K7ERQ8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000162
AC:
4
AN:
246306
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
132994
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1459578
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
725742
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsFeb 21, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;T;.
Eigen
Benign
-0.073
Eigen_PC
Benign
0.12
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.81
L;L;.
MutationTaster
Benign
0.96
D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.35
N;N;N
REVEL
Benign
0.068
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.68
T;T;T
Polyphen
0.66
P;P;.
Vest4
0.36
MutPred
0.29
Loss of methylation at R198 (P = 0.0707);Loss of methylation at R198 (P = 0.0707);.;
MVP
0.53
MPC
0.70
ClinPred
0.23
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782559570; hg19: chr17-40277859; API