Variant 3-197675081-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_014687.4(RUBCN):c.2856A>G(p.Ser952=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,250 control chromosomes in the GnomAD database, including 21,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 7425 hom., cov: 32)

Exomes 𝑓: 0.11 ( 13695 hom. )

Consequence

RUBCN
NM_014687.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -7.15

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-197675081-T-C is Benign according to our data. Variant chr3-197675081-T-C is described in ClinVar as [Benign]. Clinvar id is 129379.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-7.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUBCN	NM_014687.4 linkuse as main transcript	c.2856A>G	p.Ser952=	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.2856A>G	p.Ser952=	synonymous_variant	20/20	1	NM_014687.4	ENSP00000296343	P1	Q92622-1
RUBCN	ENST00000707076.1 linkuse as main transcript	c.2973A>G	p.Ser991=	synonymous_variant	22/22			ENSP00000516727
RUBCN	ENST00000413360.5 linkuse as main transcript	c.2742A>G	p.Ser914=	synonymous_variant	19/19	5		ENSP00000405115
RUBCN	ENST00000273582.9 linkuse as main transcript	c.2721A>G	p.Ser907=	synonymous_variant	21/21	5		ENSP00000273582		Q92622-2

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34759

AN:

152012

Hom.:

7395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.0457

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.121

AC:

29489

AN:

244102

Hom.:

3497

AF XY:

0.116

AC XY:

15457

AN XY:

133492

show subpopulations

Gnomad AFR exome

AF:

0.578

Gnomad AMR exome

AF:

0.0746

Gnomad ASJ exome

AF:

0.0997

Gnomad EAS exome

AF:

0.0400

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0642

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.112

AC:

164083

AN:

1461122

Hom.:

13695

Cov.:

AF XY:

0.111

AC XY:

80630

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.0786

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0647

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0635

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.229

AC:

34845

AN:

152128

Hom.:

7425

Cov.:

AF XY:

0.221

AC XY:

16458

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0914

Gnomad4 EAS

AF:

0.0454

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0572

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.134

Hom.:

837

Bravo

AF:

0.249

Asia WGS

AF:

0.141

AC:

491

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.109

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:1

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

-0.80

CADD

Benign

0.17

DANN

Benign

0.46

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