Variant 3-120698576-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_173825.5(RABL3):c.384-3C>T variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000361 in 1,604,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

RABL3
NM_173825.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.4569

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.08

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BP6

Variant 3-120698576-G-A is Benign according to our data. Variant chr3-120698576-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3051462.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RABL3	NM_173825.5 linkuse as main transcript	c.384-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000273375.8	NP_776186.2
RABL3	NM_001363964.1 linkuse as main transcript	c.384-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001350893.1
RABL3	NM_001363965.1 linkuse as main transcript	c.384-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001350894.1
RABL3	NR_157022.1 linkuse as main transcript	n.698-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL3	ENST00000273375.8 linkuse as main transcript	c.384-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_173825.5	ENSP00000273375	P1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000414

AC:

102

AN:

246450

Hom.:

AF XY:

0.000481

AC XY:

AN XY:

133150

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000899

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000410

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000359

AC:

522

AN:

1452628

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

283

AN XY:

722790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.000182

Gnomad4 ASJ exome

AF:

0.000732

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000412

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000354

Gnomad4 OTH exome

AF:

0.000765

GnomAD4 genome

AF:

0.000381

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000638

Hom.:

Bravo

AF:

0.000438

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00132

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RABL3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 09, 2022

This 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

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.46

dbscSNV1_RF

Benign

0.16

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