Menu
GeneBe

3-120709787-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_173825.5(RABL3):c.261C>T(p.Ser87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,607,196 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0058 ( 38 hom. )

Consequence

RABL3
NM_173825.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.157
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-120709787-G-A is Benign according to our data. Variant chr3-120709787-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.157 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 617 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RABL3NM_173825.5 linkuse as main transcriptc.261C>T p.Ser87= synonymous_variant 3/8 ENST00000273375.8
RABL3NM_001363965.1 linkuse as main transcriptc.261C>T p.Ser87= synonymous_variant 3/9
RABL3NM_001363964.1 linkuse as main transcriptc.261C>T p.Ser87= synonymous_variant 3/7
RABL3NR_157022.1 linkuse as main transcriptn.575C>T non_coding_transcript_exon_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RABL3ENST00000273375.8 linkuse as main transcriptc.261C>T p.Ser87= synonymous_variant 3/81 NM_173825.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00406
AC:
617
AN:
151982
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00295
Gnomad ASJ
AF:
0.0104
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00142
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00664
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00414
AC:
1023
AN:
247112
Hom.:
4
AF XY:
0.00412
AC XY:
551
AN XY:
133674
show subpopulations
Gnomad AFR exome
AF:
0.000866
Gnomad AMR exome
AF:
0.00174
Gnomad ASJ exome
AF:
0.0110
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000135
Gnomad FIN exome
AF:
0.00163
Gnomad NFE exome
AF:
0.00693
Gnomad OTH exome
AF:
0.00417
GnomAD4 exome
AF:
0.00577
AC:
8399
AN:
1455096
Hom.:
38
Cov.:
29
AF XY:
0.00562
AC XY:
4072
AN XY:
724006
show subpopulations
Gnomad4 AFR exome
AF:
0.000755
Gnomad4 AMR exome
AF:
0.00195
Gnomad4 ASJ exome
AF:
0.0110
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000117
Gnomad4 FIN exome
AF:
0.00199
Gnomad4 NFE exome
AF:
0.00686
Gnomad4 OTH exome
AF:
0.00464
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00406
AC:
617
AN:
152100
Hom.:
2
Cov.:
32
AF XY:
0.00394
AC XY:
293
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00123
Gnomad4 AMR
AF:
0.00295
Gnomad4 ASJ
AF:
0.0104
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00142
Gnomad4 NFE
AF:
0.00664
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00582
Hom.:
2
Bravo
AF:
0.00381
EpiCase
AF:
0.00634
EpiControl
AF:
0.00575

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2024RABL3: BP4, BP7, BS2 -
RABL3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 16, 2019This variant is classified as 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
BayesDel_noAF
Benign
-0.33
Cadd
Benign
11
Dann
Benign
0.67

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: rs35389318; hg19: chr3-120428634; COSMIC: COSV56337078; API