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3-120694208-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PS1_ModerateBP4_ModerateBP6_ModerateBS2

The NM_173825.5(RABL3):c.551G>A(p.Arg184Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00146 in 1,610,670 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

RABL3
NM_173825.5 missense

Scores

3
6
10

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.94
Variant links:
Genes affected
RABL3 (HGNC:18072): (RAB, member of RAS oncogene family like 3) Predicted to enable GTP binding activity; GTPase activity; and protein homodimerization activity. Involved in regulation of Ras protein signal transduction and regulation of protein lipidation. Predicted to be active in endomembrane system. Implicated in pancreatic cancer. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PS1
Transcript NM_173825.5 (RABL3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
BP4
Computational evidence support a benign effect (MetaRNN=0.13320854).
BP6
Variant 3-120694208-C-T is Benign according to our data. Variant chr3-120694208-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042035.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 156 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RABL3NM_173825.5 linkuse as main transcriptc.551G>A p.Arg184Gln missense_variant 6/8 ENST00000273375.8
RABL3NM_001363965.1 linkuse as main transcriptc.551G>A p.Arg184Gln missense_variant 6/9
RABL3NM_001363964.1 linkuse as main transcriptc.535-3721G>A intron_variant
RABL3NR_157022.1 linkuse as main transcriptn.865G>A non_coding_transcript_exon_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RABL3ENST00000273375.8 linkuse as main transcriptc.551G>A p.Arg184Gln missense_variant 6/81 NM_173825.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00103
AC:
156
AN:
152050
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00196
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.000677
AC:
170
AN:
251104
Hom.:
0
AF XY:
0.000678
AC XY:
92
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.00133
Gnomad OTH exome
AF:
0.000816
GnomAD4 exome
AF:
0.00150
AC:
2189
AN:
1458502
Hom.:
4
Cov.:
28
AF XY:
0.00145
AC XY:
1052
AN XY:
725570
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000113
Gnomad4 NFE exome
AF:
0.00189
Gnomad4 OTH exome
AF:
0.00108
GnomAD4 genome
AF:
0.00103
AC:
156
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.000860
AC XY:
64
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00196
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.00131
Hom.:
0
Bravo
AF:
0.000880
TwinsUK
AF:
0.00162
AC:
6
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00186
AC:
16
ExAC
AF:
0.000535
AC:
65

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

RABL3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 12, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Uncertain
-0.020
Cadd
Pathogenic
30
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.073
T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.13
T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.42
Sift
Benign
0.085
T
Sift4G
Benign
0.098
T
Polyphen
1.0
D
Vest4
0.71
MVP
0.67
MPC
0.42
ClinPred
0.14
T
GERP RS
5.7
Varity_R
0.31
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs61756477; hg19: chr3-120413055; COSMIC: COSV56337037; API