X-106773038-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_194463.2(RNF128):c.610A>T(p.Asn204Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00795 in 1,209,373 control chromosomes in the GnomAD database, including 38 homozygotes. There are 3,024 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N204K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., 142 hem., cov: 22)

Exomes 𝑓: 0.0082 ( 35 hom. 2882 hem. )

Consequence

RNF128
NM_194463.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.98

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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00972724).

BP6

Variant X-106773038-A-T is Benign according to our data. Variant chrX-106773038-A-T is described in ClinVar as [Benign]. Clinvar id is 787195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-106773038-A-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF128	NM_194463.2 link	c.610A>T	p.Asn204Tyr	missense_variant	Exon 2 of 7	ENST00000255499.3	NP_919445.1	Q8TEB7-1
RNF128	NM_024539.3 link	c.532A>T	p.Asn178Tyr	missense_variant	Exon 2 of 7		NP_078815.3	Q8TEB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF128	ENST00000255499.3 link	c.610A>T	p.Asn204Tyr	missense_variant	Exon 2 of 7	1	NM_194463.2	ENSP00000255499.2	Q8TEB7-1
RNF128	ENST00000324342.7 link	c.532A>T	p.Asn178Tyr	missense_variant	Exon 2 of 7	1		ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000418562.5 link	c.451A>T	p.Asn151Tyr	missense_variant	Exon 3 of 6	5		ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

589

AN:

111219

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.00115

Gnomad ASJ

AF:

0.0310

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.00401

GnomAD2 exomes

AF:

0.00577

AC:

1058

AN:

183393

AF XY:

0.00545

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00256

Gnomad NFE exome

AF:

0.00886

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00822

AC:

9027

AN:

1098105

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

2882

AN XY:

363503

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

AC:

AN:

26400

Gnomad4 AMR exome

AF:

0.000483

AC:

AN:

35207

Gnomad4 ASJ exome

AF:

0.0344

AC:

666

AN:

19381

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

30197

Gnomad4 SAS exome

AF:

0.0000369

AC:

AN:

54143

Gnomad4 FIN exome

AF:

0.00345

AC:

140

AN:

40530

Gnomad4 NFE exome

AF:

0.00933

AC:

7852

AN:

842018

Gnomad4 Remaining exome

AF:

0.00712

AC:

328

AN:

46092

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.00529

AC:

589

AN:

111268

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

142

AN XY:

33466

show subpopulations

Gnomad4 AFR

AF:

0.000652

AC:

0.000651763

AN:

0.000651763

Gnomad4 AMR

AF:

0.00115

AC:

0.00115285

AN:

0.00115285

Gnomad4 ASJ

AF:

0.0310

AC:

0.0309551

AN:

0.0309551

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000379

AC:

0.000379075

AN:

0.000379075

Gnomad4 FIN

AF:

0.00236

AC:

0.00235651

AN:

0.00235651

Gnomad4 NFE

AF:

0.00853

AC:

0.00852927

AN:

0.00852927

Gnomad4 OTH

AF:

0.00396

AC:

0.00396301

AN:

0.00396301

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

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:

0.00932

Hom.:

213

Bravo

AF:

0.00474

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0111

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00892

AC:

ExAC

AF:

0.00568

AC:

689

EpiCase

AF:

0.00938

EpiControl

AF:

0.00848

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;D

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;T;T

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.2

.;.;M

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.75, 0.77

MVP

0.67

MPC

1.2

ClinPred

0.024

GERP RS

5.8

Varity_R

0.87

gMVP

0.91

Mutation Taster

=70/30

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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