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GeneBe

3-120698483-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173825.5(RABL3):c.474T>C(p.His158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,614,008 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0085 ( 75 hom. )

Consequence

RABL3
NM_173825.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.81
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 -11 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=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-120698483-A-G is Benign according to our data. Variant chr3-120698483-A-G is described in ClinVar as [Benign]. Clinvar id is 3037588.Status of the report is criteria_provided_single_submitter, 1 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=2.81 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 899 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RABL3NM_173825.5 linkuse as main transcriptc.474T>C p.His158= synonymous_variant 5/8 ENST00000273375.8
RABL3NM_001363965.1 linkuse as main transcriptc.474T>C p.His158= synonymous_variant 5/9
RABL3NM_001363964.1 linkuse as main transcriptc.474T>C p.His158= synonymous_variant 5/7
RABL3NR_157022.1 linkuse as main transcriptn.788T>C non_coding_transcript_exon_variant 6/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RABL3ENST00000273375.8 linkuse as main transcriptc.474T>C p.His158= synonymous_variant 5/81 NM_173825.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00591
AC:
899
AN:
152210
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00166
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0238
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00784
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00643
AC:
1617
AN:
251344
Hom.:
11
AF XY:
0.00635
AC XY:
863
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.00160
Gnomad AMR exome
AF:
0.00127
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00170
Gnomad FIN exome
AF:
0.0246
Gnomad NFE exome
AF:
0.00818
Gnomad OTH exome
AF:
0.00489
GnomAD4 exome
AF:
0.00849
AC:
12415
AN:
1461680
Hom.:
75
Cov.:
30
AF XY:
0.00835
AC XY:
6073
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.00152
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00197
Gnomad4 FIN exome
AF:
0.0226
Gnomad4 NFE exome
AF:
0.00946
Gnomad4 OTH exome
AF:
0.00626
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00590
AC:
899
AN:
152328
Hom.:
2
Cov.:
32
AF XY:
0.00620
AC XY:
462
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.0238
Gnomad4 NFE
AF:
0.00784
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00607
Hom.:
3
Bravo
AF:
0.00406
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00524
EpiControl
AF:
0.00700

ClinVar

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

Submissions by phenotype

RABL3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 19, 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
-0.48
Cadd
Benign
7.8
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs61758778; hg19: chr3-120417330; API