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GeneBe

4-2512528-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002938.5(RNF4):c.305G>A(p.Arg102Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,166 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 0.0000066 ( 0 hom., cov: 32)

Consequence

RNF4
NM_002938.5 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2272042).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF4NM_002938.5 linkuse as main transcriptc.305G>A p.Arg102Lys missense_variant 6/8 ENST00000314289.13
RNF4NM_001185009.3 linkuse as main transcriptc.305G>A p.Arg102Lys missense_variant 7/9
RNF4XM_047416062.1 linkuse as main transcriptc.305G>A p.Arg102Lys missense_variant 7/9
RNF4NM_001185010.3 linkuse as main transcriptc.215-555G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF4ENST00000314289.13 linkuse as main transcriptc.305G>A p.Arg102Lys missense_variant 6/81 NM_002938.5 P1P78317-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 19, 2022The c.305G>A (p.R102K) alteration is located in exon 7 (coding exon 5) of the RNF4 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the arginine (R) at amino acid position 102 to be replaced by a lysine (K). 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
Benign
0.11
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.21
T;T;T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.073
FATHMM_MKL
Uncertain
0.92
D
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.6
M;.;M;M
MutationTaster
Benign
1.0
D;N;N;N;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.56
N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.10
T;T;T;T
Sift4G
Benign
0.35
T;T;T;T
Polyphen
0.0060
B;.;B;B
Vest4
0.20
MutPred
0.43
Gain of ubiquitination at R102 (P = 9e-04);Gain of ubiquitination at R102 (P = 9e-04);Gain of ubiquitination at R102 (P = 9e-04);Gain of ubiquitination at R102 (P = 9e-04);
MVP
0.66
MPC
0.51
ClinPred
0.79
D
GERP RS
3.8
Varity_R
0.14
gMVP
0.21

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.

Other links and lift over

dbSNP: rs200323065; hg19: chr4-2514255; API