Variant 3-49701516-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022064.5(RNF123):c.1303T>G(p.Phe435Val) variant causes a missense change. The variant allele was found at a frequency of 0.000252 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RNF123
NM_022064.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107106924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF123	NM_022064.5 linkuse as main transcript	c.1303T>G	p.Phe435Val	missense_variant	16/39	ENST00000327697.11
RNF123	NR_135218.2 linkuse as main transcript	n.1389T>G		non_coding_transcript_exon_variant	16/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF123	ENST00000327697.11 linkuse as main transcript	c.1303T>G	p.Phe435Val	missense_variant	16/39	1	NM_022064.5	P1	Q5XPI4-1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000291

AC:

AN:

251072

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000222

AC:

325

AN:

1461426

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

169

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000532

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000330

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000222

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.1303T>G (p.F435V) alteration is located in exon 16 (coding exon 15) of the RNF123 gene. This alteration results from a T to G substitution at nucleotide position 1303, causing the phenylalanine (F) at amino acid position 435 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Pathogenic

0.25

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.29

T;T

Eigen

Benign

0.086

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.071

T;T

Polyphen

0.85

P;P

Vest4

0.61

MVP

0.96

MPC

0.46

ClinPred

0.040

GERP RS

4.6

Varity_R

0.23

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over