Variant 3-120706004-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173825.5(RABL3):c.379A>T(p.Asn127Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000188 in 1,597,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RABL3
NM_173825.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RABL3	NM_173825.5 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	4/8	ENST00000273375.8
RABL3	NM_001363965.1 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	4/9
RABL3	NM_001363964.1 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	4/7
RABL3	NR_157022.1 linkuse as main transcript	n.693A>T		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABL3	ENST00000273375.8 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	4/8	1	NM_173825.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RABL3-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 08, 2022

The RABL3 c.379A>T variant is predicted to result in the amino acid substitution p.Asn127Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.069

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.97

D;.

Vest4

0.73

MutPred

0.44

Gain of phosphorylation at N127 (P = 0.0688);Gain of phosphorylation at N127 (P = 0.0688);

MVP

0.82

MPC

0.62

ClinPred

0.94

GERP RS

4.5

Varity_R

0.19

gMVP

0.66

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