Genetic Variant NM_194463.2:c.514G>A (chrX-106772942-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_194463.2(RNF128):c.514G>A(p.Gly172Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,207,132 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G172C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

RNF128
NM_194463.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.37

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3984416).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194463.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF128	NM_194463.2	MANE Select	c.514G>A	p.Gly172Ser	missense	Exon 2 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.436G>A	p.Gly146Ser	missense	Exon 2 of 7	NP_078815.3	Q8TEB7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF128	ENST00000255499.3	TSL:1 MANE Select	c.514G>A	p.Gly172Ser	missense	Exon 2 of 7	ENSP00000255499.2	Q8TEB7-1
RNF128	ENST00000324342.7	TSL:1	c.436G>A	p.Gly146Ser	missense	Exon 2 of 7	ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000862729.1		c.508G>A	p.Gly170Ser	missense	Exon 2 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000963

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000663

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

181393

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000737

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1096040

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

361528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26346

American (AMR)

AF:

0.0000570

AC:

AN:

35097

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19340

East Asian (EAS)

AF:

0.000298

AC:

AN:

30157

South Asian (SAS)

AF:

0.0000559

AC:

AN:

53712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40495

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000833

AC:

AN:

840741

Other (OTH)

AF:

0.00

AC:

AN:

46019

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111092

Hom.:

Cov.:

AF XY:

0.0000900

AC XY:

AN XY:

33334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30567

American (AMR)

AF:

0.0000963

AC:

AN:

10387

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.000377

AC:

AN:

2656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5907

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52956

Other (OTH)

AF:

0.000663

AC:

AN:

1508

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Laterality defects, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.033

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

PhyloP100

4.4

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.23

Sift

Benign

0.19

Sift4G

Benign

0.33

Polyphen

1.0

Vest4

0.33

MutPred

0.57

Loss of helix (P = 0.0196)

MVP

0.84

MPC

0.96

ClinPred

0.52

GERP RS

5.8

Varity_R

0.85

gMVP

0.94

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over