Variant 3-197675520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014687.4(RUBCN):c.2647-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,612,330 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

RUBCN
NM_014687.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008918

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.862

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 3-197675520-G-A is Benign according to our data. Variant chr3-197675520-G-A is described in ClinVar as [Benign]. Clinvar id is 729995.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.2647-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000296343.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RUBCN	ENST00000296343.10 linkuse as main transcript	c.2647-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_014687.4	P1	Q92622-1
RUBCN	ENST00000273582.9 linkuse as main transcript	c.2512-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5			Q92622-2
RUBCN	ENST00000413360.5 linkuse as main transcript	c.2531-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5
RUBCN	ENST00000707076.1 linkuse as main transcript	c.2764-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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

GnomAD3 exomes

AF:

0.000201

AC:

AN:

248986

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00279

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000925

AC:

135

AN:

1460030

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000978

AC:

149

AN:

152300

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.000392

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

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.00109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

7.7

Dann

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000089

dbscSNV1_RF

Benign

0.0040

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