rs145980033
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014687.4(RUBCN):c.593C>T(p.Pro198Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000697 in 1,614,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0038 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 5 hom. )
Consequence
RUBCN
NM_014687.4 missense
NM_014687.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.83
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.006392628).
BP6
Variant 3-197701842-G-A is Benign according to our data. Variant chr3-197701842-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 548452.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUBCN | NM_014687.4 | c.593C>T | p.Pro198Leu | missense_variant | 6/20 | ENST00000296343.10 | NP_055502.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUBCN | ENST00000296343.10 | c.593C>T | p.Pro198Leu | missense_variant | 6/20 | 1 | NM_014687.4 | ENSP00000296343.5 |
Frequencies
GnomAD3 genomes AF: 0.00379 AC: 577AN: 152114Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.000906 AC: 226AN: 249442Hom.: 1 AF XY: 0.000717 AC XY: 97AN XY: 135348
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GnomAD4 exome AF: 0.000369 AC: 539AN: 1461866Hom.: 5 Cov.: 32 AF XY: 0.000326 AC XY: 237AN XY: 727232
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GnomAD4 genome AF: 0.00385 AC: 586AN: 152232Hom.: 6 Cov.: 32 AF XY: 0.00392 AC XY: 292AN XY: 74428
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 19, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
0.38
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at