13-46359610-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 13/20 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUBCNL	NM_025113.5	c.1141C>G	p.Arg381Gly	missense_variant	Exon 9 of 15	ENST00000429979.6	NP_079389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUBCNL	ENST00000429979.6	c.1141C>G	p.Arg381Gly	missense_variant	Exon 9 of 15	5	NM_025113.5	ENSP00000396935.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.67	T;T;T;.;T;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.060	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.7	.;.;D;D;D;D;N;.
REVEL	Benign	0.034
Sift	Benign	0.33	.;.;T;T;T;T;T;.
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T
Polyphen		0.0, 0.0010, 0.0050	.;B;B;B;B;B;B;.
Vest4		0.10
MutPred		0.32		.;.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;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

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

Publications

LitVar

Other links and lift over

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