9-121181442-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016322.4(RAB14):​c.602G>A​(p.Arg201Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,459,020 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: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RAB14
NM_016322.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
Variant links:
Genes affected
RAB14 (HGNC:16524): (RAB14, member RAS oncogene family) RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. These proteins act as molecular switches that flip between an inactive GDP-bound state and an active GTP-bound state in which they recruit downstream effector proteins onto membranes (Junutula et al., 2004 [PubMed 15004230]).[supplied by OMIM, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2964547).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB14NM_016322.4 linkc.602G>A p.Arg201Gln missense_variant Exon 8 of 8 ENST00000373840.9 NP_057406.2 P61106A0A024R845

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB14ENST00000373840.9 linkc.602G>A p.Arg201Gln missense_variant Exon 8 of 8 1 NM_016322.4 ENSP00000362946.4 P61106

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250914
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1459020
Hom.:
0
Cov.:
31
AF XY:
0.00000827
AC XY:
6
AN XY:
725708
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.602G>A (p.R201Q) alteration is located in exon 8 (coding exon 7) of the RAB14 gene. This alteration results from a G to A substitution at nucleotide position 602, causing the arginine (R) at amino acid position 201 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
0.085
BayesDel_addAF
Benign
0.00079
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.071
T
Eigen
Benign
-0.084
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.010
N
REVEL
Benign
0.20
Sift
Benign
0.35
T
Sift4G
Benign
0.70
T
Polyphen
0.0
B
Vest4
0.59
MutPred
0.25
Gain of sheet (P = 0.039);
MVP
0.82
MPC
0.31
ClinPred
0.30
T
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.096
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs771312021; hg19: chr9-123943720; COSMIC: COSV53045249; COSMIC: COSV53045249; API