Variant 3-120698483-A-G details in Genebe, Genetics Data Aggregator

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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 75 hom. )

Consequence

RABL3
NM_173825.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

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]

RABL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 3-120698483-A-G is Benign according to our data. Variant chr3-120698483-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3037588.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.81 with no splicing effect.

BS2

High AC in GnomAd4 at 899 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RABL3	NM_173825.5 linkuse as main transcript	c.474T>C	p.His158=	synonymous_variant	5/8	ENST00000273375.8	NP_776186.2
RABL3	NM_001363965.1 linkuse as main transcript	c.474T>C	p.His158=	synonymous_variant	5/9		NP_001350894.1
RABL3	NM_001363964.1 linkuse as main transcript	c.474T>C	p.His158=	synonymous_variant	5/7		NP_001350893.1
RABL3	NR_157022.1 linkuse as main transcript	n.788T>C		non_coding_transcript_exon_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL3	ENST00000273375.8 linkuse as main transcript	c.474T>C	p.His158=	synonymous_variant	5/8	1	NM_173825.5	ENSP00000273375	P1

Frequencies

GnomAD3 genomes

AF:

0.00591

AC:

899

AN:

152210

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00590

AC:

899

AN:

152328

Hom.:

Cov.:

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.:

Bravo

AF:

0.00406

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00524

EpiControl

AF:

0.00700

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

RABL3: BP4, BP7, BS2 -

RABL3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over