Variant X-106787984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The ENST00000255499.3(RNF128):c.871C>T(p.Arg291Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,143,352 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.000017 ( 0 hom. 4 hem. )

Consequence

RNF128
ENST00000255499.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

RNF128 (HGNC:21153): (ring finger protein 128) The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

RNF128 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.869

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_194463.2 linkuse as main transcript	c.871C>T	p.Arg291Cys	missense_variant	4/7	ENST00000255499.3	NP_919445.1	Q8TEB7-1
RNF128	NM_024539.3 linkuse as main transcript	c.793C>T	p.Arg265Cys	missense_variant	4/7		NP_078815.3	Q8TEB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF128	ENST00000255499.3 linkuse as main transcript	c.871C>T	p.Arg291Cys	missense_variant	4/7	1	NM_194463.2	ENSP00000255499.2	Q8TEB7-1
RNF128	ENST00000324342.7 linkuse as main transcript	c.793C>T	p.Arg265Cys	missense_variant	4/7	1		ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000418562.5 linkuse as main transcript	c.712C>T	p.Arg238Cys	missense_variant	5/6	5		ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes

AF:

0.00000923

AC:

AN:

108401

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31047

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000192

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

152572

Hom.:

AF XY:

0.0000201

AC XY:

AN XY:

49678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000990

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1034951

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

317161

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000368

Gnomad4 SAS exome

AF:

0.0000457

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000149

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000923

AC:

AN:

108401

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31047

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000192

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

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

Mar 06, 2023

The c.871C>T (p.R291C) alteration is located in exon 4 (coding exon 4) of the RNF128 gene. This alteration results from a C to T substitution at nucleotide position 871, causing the arginine (R) at amino acid position 291 to be replaced by a cysteine (C). 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

0.91

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Pathogenic

0.77

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.1

.;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.81, 0.86

MutPred

0.69

.;.;Gain of sheet (P = 0.0827);

MVP

0.89

MPC

1.3

ClinPred

0.96

GERP RS

5.3

Varity_R

0.63

gMVP

0.75

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