Variant 3-197675186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_014687.4(RUBCN):c.2751G>A(p.Ala917=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

RUBCN
NM_014687.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.44

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-197675186-C-T is Benign according to our data. Variant chr3-197675186-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUBCN	NM_014687.4 linkuse as main transcript	c.2751G>A	p.Ala917=	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.2751G>A	p.Ala917=	synonymous_variant	20/20	1	NM_014687.4	ENSP00000296343	P1	Q92622-1
RUBCN	ENST00000707076.1 linkuse as main transcript	c.2868G>A	p.Ala956=	synonymous_variant	22/22			ENSP00000516727
RUBCN	ENST00000413360.5 linkuse as main transcript	c.2637G>A	p.Ala879=	synonymous_variant	19/19	5		ENSP00000405115
RUBCN	ENST00000273582.9 linkuse as main transcript	c.2616G>A	p.Ala872=	synonymous_variant	21/21	5		ENSP00000273582		Q92622-2

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000925

AC:

228

AN:

246358

Hom.:

AF XY:

0.000947

AC XY:

127

AN XY:

134156

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.000996

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000896

AC:

1310

AN:

1461722

Hom.:

Cov.:

AF XY:

0.000880

AC XY:

640

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00423

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000394

Gnomad4 NFE exome

AF:

0.000810

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000584

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000867

Hom.:

Bravo

AF:

0.000756

EpiCase

AF:

0.00142

EpiControl

AF:

0.00160

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	RUBCN: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.2

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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