Variant 3-197676908-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014687.4(RUBCN):c.2623G>A(p.Ala875Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000738 in 1,614,192 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 2 hom. )

Consequence

RUBCN
NM_014687.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.750

Variant links:

Genes affected

RUBCN (HGNC:28991): (rubicon autophagy regulator) The protein encoded by this gene is a negative regulator of autophagy and endocytic trafficking and controls endosome maturation. This protein contains two conserved domains, an N-terminal RUN domain and a C-terminal DUF4206 domain. The RUN domain is involved in Ras-like GTPase signaling, and the DUF4206 domain contains a diacylglycerol (DAG) binding-like motif. Mutation in this gene results in deletion of the DAG binding-like motif and causes a recessive ataxia. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

RUBCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052256286).

BP6

Variant 3-197676908-C-T is Benign according to our data. Variant chr3-197676908-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042841.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUBCN	NM_014687.4 linkuse as main transcript	c.2623G>A	p.Ala875Thr	missense_variant	18/20	ENST00000296343.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUBCN	ENST00000296343.10 linkuse as main transcript	c.2623G>A	p.Ala875Thr	missense_variant	18/20	1	NM_014687.4	P1	Q92622-1

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

131

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000769

AC:

192

AN:

249554

Hom.:

AF XY:

0.000879

AC XY:

119

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00524

Gnomad NFE exome

AF:

0.000503

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000726

AC:

1061

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

534

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000715

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00530

Gnomad4 NFE exome

AF:

0.000631

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000860

AC:

131

AN:

152308

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000841

AC:

ExAC

AF:

0.000744

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RUBCN-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2020

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.67

Eigen

Benign

-0.073

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.69

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.016

Sift

Benign

0.82

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;B

Vest4

0.11

MVP

0.42

MPC

0.34

ClinPred

0.0095

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.31

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