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GeneBe

4-2512457-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 13/21 in silico tools predict 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: 0.000039 ( 1 hom. )

Consequence

RNF4
NM_002938.5 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.824
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=0.14425924).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF4NM_002938.5 linkuse as main transcriptc.234G>T p.Arg78Ser missense_variant 6/8 ENST00000314289.13
RNF4NM_001185009.3 linkuse as main transcriptc.234G>T p.Arg78Ser missense_variant 7/9
RNF4XM_047416062.1 linkuse as main transcriptc.234G>T p.Arg78Ser missense_variant 7/9
RNF4NM_001185010.3 linkuse as main transcriptc.214+492G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF4ENST00000314289.13 linkuse as main transcriptc.234G>T p.Arg78Ser missense_variant 6/81 NM_002938.5 P1P78317-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152126
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000203
AC:
5
AN:
246050
Hom.:
0
AF XY:
0.0000300
AC XY:
4
AN XY:
133462
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 SAS 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:
57
AN:
1460076
Hom.:
1
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
726190
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
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:
0.0000422
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.000238
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000826
AC:
1

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 13, 2021The c.234G>T (p.R78S) alteration is located in exon 7 (coding exon 5) of the RNF4 gene. This alteration results from a G to T substitution at nucleotide position 234, causing the arginine (R) at amino acid position 78 to be replaced by a serine (S). 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
0.45
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.29
Cadd
Benign
21
Dann
Benign
0.95
DEOGEN2
Benign
0.12
T;T;T;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.86
D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.7
L;.;L;L
MutationTaster
Benign
0.69
D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.21
T;T;T;T
Sift4G
Benign
0.53
T;T;T;T
Polyphen
0.96
D;.;D;D
Vest4
0.61
MutPred
0.35
Loss of glycosylation at P76 (P = 0.0075);Loss of glycosylation at P76 (P = 0.0075);Loss of glycosylation at P76 (P = 0.0075);Loss of glycosylation at P76 (P = 0.0075);
MVP
0.77
MPC
0.56
ClinPred
0.23
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.21
gMVP
0.49

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: rs377600326; hg19: chr4-2514184; API