dbSNP rs967219053: RNF128:p.Arg19Ser (chrX-106726970-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_194463.2(RNF128):c.57A>T(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,080,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000083 ( 0 hom. 2 hem. )

Consequence

RNF128
NM_194463.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.499

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1091426).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF128	NM_194463.2 link	c.57A>T	p.Arg19Ser	missense_variant	Exon 1 of 7	ENST00000255499.3	NP_919445.1	Q8TEB7-1
RNF128	NM_024539.3 link	c.406+32562A>T		intron_variant	Intron 1 of 6		NP_078815.3	Q8TEB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF128	ENST00000255499.3 link	c.57A>T	p.Arg19Ser	missense_variant	Exon 1 of 7	1	NM_194463.2	ENSP00000255499.2	Q8TEB7-1
RNF128	ENST00000324342.7 link	c.406+32562A>T		intron_variant	Intron 1 of 6	1		ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000418562.5 link	c.325+32562A>T		intron_variant	Intron 2 of 5	5		ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

142933

Hom.:

AF XY:

0.00

AC XY:

AN XY:

43549

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000423

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:

0.0000336

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000833

AC:

AN:

1080833

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

352377

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000308

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000959

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.57A>T (p.R19S) alteration is located in exon 1 (coding exon 1) of the RNF128 gene. This alteration results from a A to T substitution at nucleotide position 57, causing the arginine (R) at amino acid position 19 to be replaced by a serine (S). 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

Benign

0.23

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.090

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.61

M_CAP

Benign

0.037

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.11

REVEL

Benign

0.25

Sift

Benign

0.41

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.26

MutPred

0.71

Loss of MoRF binding (P = 0.0606);

MVP

0.68

MPC

0.37

ClinPred

0.019

GERP RS

1.8

Varity_R

0.098

gMVP

0.70

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