Variant 3-120709774-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000273375.8(RABL3):c.268+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,598,902 control chromosomes in the GnomAD database, including 79,708 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6272 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73436 hom. )

Consequence

RABL3
ENST00000273375.8 splice_region, intron

Scores

Splicing: ADA: 0.0001029

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0730

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:

RABL3 (HGNC:):

RABL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-120709774-T-C is Benign according to our data. Variant chr3-120709774-T-C is described in ClinVar as [Benign]. Clinvar id is 3059517.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RABL3	NM_173825.5 linkuse as main transcript	c.268+6A>G	splice_region_variant, intron_variant	ENST00000273375.8	NP_776186.2	Q5HYI8
RABL3	NM_001363965.1 linkuse as main transcript	c.268+6A>G	splice_region_variant, intron_variant		NP_001350894.1
RABL3	NM_001363964.1 linkuse as main transcript	c.268+6A>G	splice_region_variant, intron_variant		NP_001350893.1
RABL3	NR_157022.1 linkuse as main transcript	n.582+6A>G	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL3	ENST00000273375.8 linkuse as main transcript	c.268+6A>G		splice_region_variant, intron_variant		1	NM_173825.5	ENSP00000273375.4		Q5HYI8

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41899

AN:

151724

Hom.:

6266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.276

AC:

67139

AN:

243558

Hom.:

10319

AF XY:

0.276

AC XY:

36344

AN XY:

131768

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.311

AC:

450282

AN:

1447060

Hom.:

73436

Cov.:

AF XY:

0.306

AC XY:

220744

AN XY:

720334

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.276

AC:

41929

AN:

151842

Hom.:

6272

Cov.:

AF XY:

0.279

AC XY:

20685

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.318

Hom.:

7675

Bravo

AF:

0.259

Asia WGS

AF:

0.168

AC:

585

AN:

3478

EpiCase

AF:

0.322

EpiControl

AF:

0.321

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RABL3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 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

-0.84

CADD

Benign

6.1

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0020

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