dbSNP rs767581575: RUBCNL:p.Leu245Val (chr13-46368135-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025113.5(RUBCNL):c.733C>G(p.Leu245Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

RUBCNL
NM_025113.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.332

Publications

0 publications found

Variant links:

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]

RUBCNL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.017314047).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUBCNL	NM_025113.5	MANE Select	c.733C>G	p.Leu245Val	missense	Exon 5 of 15	NP_079389.2	Q9H714-5
RUBCNL	NM_001286761.2		c.733C>G	p.Leu245Val	missense	Exon 5 of 15	NP_001273690.1	Q9H714-5
RUBCNL	NM_001349772.2		c.733C>G	p.Leu245Val	missense	Exon 4 of 14	NP_001336701.1	Q9H714-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUBCNL	ENST00000429979.6	TSL:5 MANE Select	c.733C>G	p.Leu245Val	missense	Exon 5 of 15	ENSP00000396935.1	Q9H714-5
RUBCNL	ENST00000378784.8	TSL:1	c.532C>G	p.Leu178Val	missense	Exon 5 of 15	ENSP00000368061.4	Q9H714-3
RUBCNL	ENST00000378797.6	TSL:1	c.88C>G	p.Leu30Val	missense	Exon 3 of 13	ENSP00000368074.3	A0A0A0MRV7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000756

AC:

AN:

251158

AF XY:

0.0000663

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111854

Other (OTH)

AF:

0.0000828

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.8

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.62

M_CAP

Benign

0.0090

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

PhyloP100

0.33

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.78

REVEL

Benign

0.039

Sift

Benign

0.41

Sift4G

Benign

0.63

Polyphen

0.45

Vest4

0.10

MutPred

0.14

Gain of glycosylation at S242 (P = 0.0853)

MVP

0.11

MPC

0.050

ClinPred

0.030

GERP RS

1.3

Varity_R

0.034

gMVP

0.10

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over