Variant 3-120709787-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

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

Clinical Significance

Likely benign criteria provided, single submitter 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]

RABL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

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_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.157 with no splicing effect.

BS2

High AC in GnomAd4 at 617 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RABL3	NM_173825.5 linkuse as main transcript	c.261C>T	p.Ser87=	synonymous_variant	3/8	ENST00000273375.8	NP_776186.2
RABL3	NM_001363965.1 linkuse as main transcript	c.261C>T	p.Ser87=	synonymous_variant	3/9		NP_001350894.1
RABL3	NM_001363964.1 linkuse as main transcript	c.261C>T	p.Ser87=	synonymous_variant	3/7		NP_001350893.1
RABL3	NR_157022.1 linkuse as main transcript	n.575C>T		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL3	ENST00000273375.8 linkuse as main transcript	c.261C>T	p.Ser87=	synonymous_variant	3/8	1	NM_173825.5	ENSP00000273375	P1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

617

AN:

151982

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00406

AC:

617

AN:

152100

Hom.:

Cov.:

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.:

Bravo

AF:

0.00381

EpiCase

AF:

0.00634

EpiControl

AF:

0.00575

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

Jan 01, 2024

RABL3: BP4, BP7, BS2 -

RABL3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 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

-0.33

CADD

Benign

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.

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