Genetic Variant RNF4:p.Arg78Ser (chr4-2512457-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002938.5(RNF4):c.234G>T(p.Arg78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,612,320 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 1 hom. )

Consequence

RNF4
NM_002938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.824

Publications

0 publications found

Variant links:

Genes affected

RNF4 (HGNC:10067): (ring finger protein 4) The protein encoded by this gene contains a RING finger motif and acts as a transcription regulator. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of GATA-mediated transcription. Transcription repressor ZNF278/PATZ is found to interact with this protein, and thus reduce the enhancement of androgen receptor-dependent transcription mediated by this protein. Studies of the mouse and rat counterparts suggested a role of this protein in spermatogenesis. A pseudogene of this gene is found on chromosome 1.[provided by RefSeq, Jul 2010]

RNF4 links:

ENSG00000290180 (HGNC:):

ENSG00000290180 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14425924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002938.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF4	NM_002938.5	MANE Select	c.234G>T	p.Arg78Ser	missense	Exon 6 of 8	NP_002929.1	P78317-1
RNF4	NM_001185009.3		c.234G>T	p.Arg78Ser	missense	Exon 7 of 9	NP_001171938.1	P78317-1
RNF4	NM_001185010.3		c.214+492G>T		intron	N/A	NP_001171939.1	P78317-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF4	ENST00000314289.13	TSL:1 MANE Select	c.234G>T	p.Arg78Ser	missense	Exon 6 of 8	ENSP00000315212.8	P78317-1
RNF4	ENST00000506706.5	TSL:1	c.234G>T	p.Arg78Ser	missense	Exon 7 of 9	ENSP00000424076.1	P78317-1
RNF4	ENST00000511859.5	TSL:1	c.214+492G>T		intron	N/A	ENSP00000426615.1	P78317-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000203

AC:

AN:

246050

AF XY:

0.0000300

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1460076

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

726190

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44384

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.0000465

AC:

AN:

85986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111158

Other (OTH)

AF:

0.0000829

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000394

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41546

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000521

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000238

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.12

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.69

M_CAP

Benign

0.026

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.7

PhyloP100

0.82

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.1

REVEL

Benign

0.23

Sift

Benign

0.21

Sift4G

Benign

0.53

Polyphen

0.96

Vest4

0.61

MutPred

0.35

Loss of glycosylation at P76 (P = 0.0075)

MVP

0.77

MPC

0.56

ClinPred

0.23

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.21

gMVP

0.49

Mutation Taster

=65/35

polymorphism

(source)

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

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