13-46359610-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025113.5(RUBCNL):​c.1141C>G​(p.Arg381Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RUBCNL NM_025113.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05984515).

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>G	p.Arg381Gly	missense	Exon 9 of 15	NP_079389.2	Q9H714-5
	RUBCNL	NM_001286761.2		c.1141C>G	p.Arg381Gly	missense	Exon 9 of 15	NP_001273690.1	Q9H714-5
	RUBCNL	NM_001349772.2		c.1141C>G	p.Arg381Gly	missense	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>G	p.Arg381Gly	missense	Exon 9 of 15	ENSP00000396935.1	Q9H714-5
	RUBCNL	ENST00000378784.8	TSL:1	c.940C>G	p.Arg314Gly	missense	Exon 9 of 15	ENSP00000368061.4	Q9H714-3
	RUBCNL	ENST00000378797.6	TSL:1	c.496C>G	p.Arg166Gly	missense	Exon 7 of 13	ENSP00000368074.3	A0A0A0MRV7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436440 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712478

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.00 AC: 0 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: 9.11e-7 AC: 1 AN: 1098164

Other (OTH) AF: 0.00 AC: 0 AN: 59358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.3
DANN	Benign	0.87
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.034
Sift	Benign	0.33	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.32		Loss of helix (P = 0.0558)
MVP		0.14
MPC		0.036
ClinPred		0.061	T
GERP RS		3.5
Varity_R		0.061
gMVP		0.18
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs193920942; hg19: chr13-46933745; COSMIC: COSV100528968;