rs193920942

Variant names:

• chr13-46359610-G-A
• rs193920942
• NM_025113.5:c.1141C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-46359610-G-A
• chr13-46359610-G-C
• chr13-46359610-G-T

Variant summary

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

The NM_025113.5(RUBCNL):​c.1141C>T​(p.Arg381*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,588,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: RUBCNL NM_025113.5 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

Genes affected

RUBCNL (HGNC:20420): (rubicon like autophagy enhancer) This gene encodes a cysteine-rich protein that contains a putative zinc-RING and/or ribbon domain. The encoded protein is related to Run domain Beclin-1-interacting and cysteine-rich domain-containing protein, which plays a role in endocytic trafficking and autophagy. In cervical cancer cell lines, this gene is expressed at low levels and may function as a tumor suppressor. Promoter hypermethylation of this gene is observed in cervical cancer cell lines and tissue derived from human patients. [provided by RefSeq, Mar 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025113.5. 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
	RUBCNL	NM_025113.5	MANE Select	c.1141C>T	p.Arg381*	stop_gained	Exon 9 of 15	NP_079389.2	Q9H714-5
	RUBCNL	NM_001286761.2		c.1141C>T	p.Arg381*	stop_gained	Exon 9 of 15	NP_001273690.1	Q9H714-5
	RUBCNL	NM_001349772.2		c.1141C>T	p.Arg381*	stop_gained	Exon 8 of 14	NP_001336701.1	Q9H714-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUBCNL	ENST00000429979.6	TSL:5 MANE Select	c.1141C>T	p.Arg381*	stop_gained	Exon 9 of 15	ENSP00000396935.1	Q9H714-5
	RUBCNL	ENST00000378784.8	TSL:1	c.940C>T	p.Arg314*	stop_gained	Exon 9 of 15	ENSP00000368061.4	Q9H714-3
	RUBCNL	ENST00000378797.6	TSL:1	c.496C>T	p.Arg166*	stop_gained	Exon 7 of 13	ENSP00000368074.3	A0A0A0MRV7

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151794 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

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

GnomAD2 exomes AF: 0.000128 AC: 28 AN: 218712 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00159

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000208

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000244 AC: 35 AN: 1436440 Hom.: 0 Cov.: 30 AF XY: 0.0000211 AC XY: 15 AN XY: 712478

African (AFR) AF: 0.0000906 AC: 3 AN: 33108

American (AMR) AF: 0.00 AC: 0 AN: 41230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25478

East Asian (EAS) AF: 0.000512 AC: 20 AN: 39078

South Asian (SAS) AF: 0.0000243 AC: 2 AN: 82374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000820 AC: 9 AN: 1098164

Other (OTH) AF: 0.0000168 AC: 1 AN: 59358

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151912 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74208

African (AFR) AF: 0.0000725 AC: 3 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000907 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	34
DANN	Uncertain	1.0
Eigen	Benign	0.038
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.15	N
PhyloP100		1.5
Vest4		0.38
GERP RS		3.5
Mutation Taster		=28/172	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs193920942; hg19: chr13-46933745; COSMIC: COSV59794894;