3-197701841-CG-GA

Variant names:

• chr3-197701841-CG-GA
• NM_014687.4:c.593_594delCGinsTC
• RUBCN p.Pro198Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014687.4(RUBCN):​c.593_594delCGinsTC​(p.Pro198Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P198P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUBCN NM_014687.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 15

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014687.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUBCN	NM_014687.4	MANE Select	c.593_594delCGinsTC	p.Pro198Leu	missense	N/A	NP_055502.1	Q92622-1
	RUBCN	NM_001346873.2		c.593_594delCGinsTC	p.Pro198Leu	missense	N/A	NP_001333802.1	A0A9L9PY84
	RUBCN	NM_001145642.5		c.413_414delCGinsTC	p.Pro138Leu	missense	N/A	NP_001139114.1	Q92622-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUBCN	ENST00000296343.10	TSL:1 MANE Select	c.593_594delCGinsTC	p.Pro198Leu	missense	N/A	ENSP00000296343.5	Q92622-1
	RUBCN	ENST00000449205.1	TSL:1	c.593_594delCGinsTC	p.Pro198Leu	missense	N/A	ENSP00000390962.1	E9PEM3
	RUBCN	ENST00000707076.1		c.593_594delCGinsTC	p.Pro198Leu	missense	N/A	ENSP00000516727.1	A0A9L9PY84

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-197428712;