Variant X-106694345-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The ENST00000324342.7(RNF128):c.343G>A(p.Asp115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,094,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000013 ( 0 hom. 7 hem. )

Consequence

RNF128
ENST00000324342.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.243

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11309904).

BP6

Variant X-106694345-G-A is Benign according to our data. Variant chrX-106694345-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206019.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-106694345-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_024539.3 linkuse as main transcript	c.343G>A	p.Asp115Asn	missense_variant	1/7		NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000324342.7 linkuse as main transcript	c.343G>A	p.Asp115Asn	missense_variant	1/7	1		ENSP00000316127	A1	Q8TEB7-2
RNF128	ENST00000418562.5 linkuse as main transcript	c.262G>A	p.Asp88Asn	missense_variant	2/6	5		ENSP00000412610

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177548

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

62582

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000251

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1094631

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

360323

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.99

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

T;.

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.054

Sift

Benign

0.34

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

.;B

Vest4

0.10

MutPred

0.56

.;Loss of stability (P = 0.0406);

MVP

0.25

ClinPred

0.024

GERP RS

3.4

Splicing

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