Variant 3-49712543-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022064.5(RNF123):c.2561G>A(p.Arg854His) variant causes a missense change. The variant allele was found at a frequency of 0.0905 in 1,614,116 control chromosomes in the GnomAD database, including 7,270 homozygotes. 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.070 ( 509 hom., cov: 33)

Exomes 𝑓: 0.093 ( 6761 hom. )

Consequence

RNF123
NM_022064.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

RNF123 (HGNC:21148): (ring finger protein 123) The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RNF123 links:

RNF123 (HGNC:):

RNF123 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002419144).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF123	NM_022064.5 linkuse as main transcript	c.2561G>A	p.Arg854His	missense_variant	27/39	ENST00000327697.11	NP_071347.2	Q5XPI4-1
RNF123	NR_135218.2 linkuse as main transcript	n.2651G>A		non_coding_transcript_exon_variant	27/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF123	ENST00000327697.11 linkuse as main transcript	c.2561G>A	p.Arg854His	missense_variant	27/39	1	NM_022064.5	ENSP00000328287.6		Q5XPI4-1

Frequencies

GnomAD3 genomes

AF:

0.0697

AC:

10603

AN:

152170

Hom.:

509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.0957

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0985

Gnomad OTH

AF:

0.0757

GnomAD3 exomes

AF:

0.0775

AC:

19485

AN:

251388

Hom.:

895

AF XY:

0.0785

AC XY:

10665

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.0266

Gnomad SAS exome

AF:

0.0530

Gnomad FIN exome

AF:

0.0972

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0846

GnomAD4 exome

AF:

0.0926

AC:

135422

AN:

1461828

Hom.:

6761

Cov.:

AF XY:

0.0915

AC XY:

66528

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.0485

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.0201

Gnomad4 SAS exome

AF:

0.0541

Gnomad4 FIN exome

AF:

0.0960

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0860

GnomAD4 genome

AF:

0.0696

AC:

10603

AN:

152288

Hom.:

509

Cov.:

AF XY:

0.0693

AC XY:

5162

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.0632

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.0564

Gnomad4 FIN

AF:

0.0957

Gnomad4 NFE

AF:

0.0985

Gnomad4 OTH

AF:

0.0744

Alfa

AF:

0.0936

Hom.:

1176

Bravo

AF:

0.0654

TwinsUK

AF:

0.109

AC:

404

ALSPAC

AF:

0.101

AC:

390

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.102

AC:

880

ExAC

AF:

0.0764

AC:

9273

Asia WGS

AF:

0.0310

AC:

111

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

0.078

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.22

Sift

Benign

0.097

T;T

Sift4G

Benign

0.30

T;D

Polyphen

0.99

D;D

Vest4

0.18

MPC

0.32

ClinPred

0.018

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over