Variant chr3-197675039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014687.4(RUBCN):c.2898C>T(p.Ala966=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,612,738 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 5 hom. )

Consequence

RUBCN
NM_014687.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0930

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-197675039-G-A is Benign according to our data. Variant chr3-197675039-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 791392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-197675039-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUBCN	NM_014687.4 linkuse as main transcript	c.2898C>T	p.Ala966=	synonymous_variant	20/20	ENST00000296343.10	NP_055502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUBCN	ENST00000296343.10 linkuse as main transcript	c.2898C>T	p.Ala966=	synonymous_variant	20/20	1	NM_014687.4	ENSP00000296343	P1	Q92622-1
RUBCN	ENST00000707076.1 linkuse as main transcript	c.3015C>T	p.Ala1005=	synonymous_variant	22/22			ENSP00000516727
RUBCN	ENST00000413360.5 linkuse as main transcript	c.2784C>T	p.Ala928=	synonymous_variant	19/19	5		ENSP00000405115
RUBCN	ENST00000273582.9 linkuse as main transcript	c.2763C>T	p.Ala921=	synonymous_variant	21/21	5		ENSP00000273582		Q92622-2

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

276

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00139

AC:

337

AN:

242880

Hom.:

AF XY:

0.00148

AC XY:

197

AN XY:

132950

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.000605

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00284

AC:

4151

AN:

1460430

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

2085

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.000153

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00181

AC:

276

AN:

152308

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

112

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00214

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	RUBCN: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.1

DANN

Benign

0.77

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