Variant 3-120689896-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_173825.5(RABL3):c.646-8G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,609,376 control chromosomes in the GnomAD database, including 35 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 0.0030 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 31 hom. )

Consequence

RABL3
NM_173825.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001018

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.316

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=-0.49).

BP6

Variant 3-120689896-C-G is Benign according to our data. Variant chr3-120689896-C-G is described in ClinVar as [Benign]. Clinvar id is 3037805.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RABL3	NM_173825.5 linkuse as main transcript	c.646-8G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000273375.8	NP_776186.2
RABL3	NM_001363964.1 linkuse as main transcript	c.574-8G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001350893.1
RABL3	NM_001363965.1 linkuse as main transcript	c.688-8G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001350894.1
RABL3	NR_157022.1 linkuse as main transcript	n.960-8G>C	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.646-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_173825.5	ENSP00000273375	P1

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

460

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00323

AC:

810

AN:

250424

Hom.:

AF XY:

0.00297

AC XY:

402

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0284

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00158

AC:

2309

AN:

1457220

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1155

AN XY:

725364

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.000613

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152156

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0284

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.000529

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

Jan 03, 2020

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

-0.49

CADD

Benign

5.3

DANN

Benign

0.79

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