Variant chrX-106727370-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_194463.2(RNF128):c.457A>G(p.Asn153Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000819 in 1,208,710 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000087 ( 0 hom. 28 hem. )

Consequence

RNF128
NM_194463.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29532632).

BS2

High Hemizygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_194463.2 link	c.457A>G	p.Asn153Asp	missense_variant	1/7	ENST00000255499.3	NP_919445.1	Q8TEB7-1
RNF128	NM_024539.3 link	c.406+32962A>G		intron_variant			NP_078815.3	Q8TEB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF128	ENST00000255499.3 link	c.457A>G	p.Asn153Asp	missense_variant	1/7	1	NM_194463.2	ENSP00000255499.2	Q8TEB7-1
RNF128	ENST00000324342.7 link	c.406+32962A>G		intron_variant		1		ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000418562.5 link	c.325+32962A>G		intron_variant		5		ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes

AF:

0.0000362

AC:

AN:

110522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32816

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:

0.0000759

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000384

AC:

AN:

182327

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67281

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000730

Gnomad ASJ exome

AF:

0.000535

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000865

AC:

AN:

1098188

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

363546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.000671

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000879

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000362

AC:

AN:

110522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32816

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:

0.0000759

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

May 23, 2023

The c.457A>G (p.N153D) alteration is located in exon 1 (coding exon 1) of the RNF128 gene. This alteration results from a A to G substitution at nucleotide position 457, causing the asparagine (N) at amino acid position 153 to be replaced by an aspartic acid (D). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.75

M_CAP

Benign

0.048

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.44

Vest4

0.46

MutPred

0.49

Gain of phosphorylation at T151 (P = 0.1213);

MVP

0.56

MPC

0.84

ClinPred

0.32

GERP RS

4.5

Varity_R

0.85

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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