4-2497014-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002938.5(RNF4):c.17G>A(p.Arg6His) variant causes a missense change. The variant allele was found at a frequency of 0.0000281 in 1,599,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RNF4
NM_002938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3075129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RNF4	NM_002938.5 link	c.17G>A	p.Arg6His	missense_variant	Exon 3 of 8	ENST00000314289.13	NP_002929.1
RNF4	NM_001185009.3 link	c.17G>A	p.Arg6His	missense_variant	Exon 4 of 9		NP_001171938.1
RNF4	NM_001185010.3 link	c.17G>A	p.Arg6His	missense_variant	Exon 3 of 7		NP_001171939.1
RNF4	XM_047416062.1 link	c.17G>A	p.Arg6His	missense_variant	Exon 4 of 9		XP_047272018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF4	ENST00000314289.13 link	c.17G>A	p.Arg6His	missense_variant	Exon 3 of 8	1	NM_002938.5	ENSP00000315212.8		P78317-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152092

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:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

227250

Hom.:

AF XY:

0.00000817

AC XY:

AN XY:

122446

show subpopulations

Gnomad AFR exome

AF:

0.0000720

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:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000269

AC:

AN:

1447394

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

718482

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000344

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17G>A (p.R6H) alteration is located in exon 4 (coding exon 2) of the RNF4 gene. This alteration results from a G to A substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a histidine (H). 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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;T;.;T;.;.;.;T;T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

T;.;T;T;T;T;.;.;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.31

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

.;L;L;.;.;.;L;L;L;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.1

D;N;N;N;D;D;D;N;N;D

REVEL

Benign

0.12

Sift

Benign

0.12

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0030, 0.39

.;B;.;.;.;B;.;B;B;.

Vest4

0.69, 0.68, 0.63

MutPred

0.42

Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);Gain of glycosylation at T3 (P = 0.0039);

MVP

0.89

MPC

0.61

ClinPred

0.74

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.35

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