Variant 13-46371941-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_025113.5(RUBCNL):c.535G>C(p.Gly179Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000672 in 1,613,676 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 14 hom. )

Consequence

RUBCNL
NM_025113.5 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 13-46371941-C-G is Benign according to our data. Variant chr13-46371941-C-G is described in ClinVar as [Benign]. Clinvar id is 715525.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00067 (102/152298) while in subpopulation EAS AF= 0.018 (93/5178). AF 95% confidence interval is 0.015. There are 2 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUBCNL	NM_025113.5 linkuse as main transcript	c.535G>C	p.Gly179Arg	missense_variant, splice_region_variant	3/15	ENST00000429979.6	NP_079389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUBCNL	ENST00000429979.6 linkuse as main transcript	c.535G>C	p.Gly179Arg	missense_variant, splice_region_variant	3/15	5	NM_025113.5	ENSP00000396935	A2	Q9H714-5

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

250230

Hom.:

AF XY:

0.00112

AC XY:

151

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0165

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000673

AC:

983

AN:

1461378

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

441

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152298

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0180

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000767

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;T;.;.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.70

T;.;T;T;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

0.64

D;D;D;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.1

D;D;D;D;.;D

REVEL

Benign

0.052

Sift

Benign

0.087

T;T;T;T;.;T

Sift4G

Uncertain

0.0090

D;D;D;D;D;.

Polyphen

0.086

B;B;B;B;.;.

Vest4

0.39

MVP

0.42

MPC

0.037

ClinPred

0.048

GERP RS

4.8

Varity_R

0.23

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.85

SpliceAI score (max)

0.69

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.69

Position offset: 0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over