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GeneBe

4-2497044-C-T

Variant summary

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

The NM_002938.5(RNF4):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RNF4
NM_002938.5 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10
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]

Genome browser will be placed here

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=0.15977556).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF4NM_002938.5 linkuse as main transcriptc.47C>T p.Ala16Val missense_variant 3/8 ENST00000314289.13
RNF4NM_001185009.3 linkuse as main transcriptc.47C>T p.Ala16Val missense_variant 4/9
RNF4NM_001185010.3 linkuse as main transcriptc.47C>T p.Ala16Val missense_variant 3/7
RNF4XM_047416062.1 linkuse as main transcriptc.47C>T p.Ala16Val missense_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF4ENST00000314289.13 linkuse as main transcriptc.47C>T p.Ala16Val missense_variant 3/81 NM_002938.5 P1P78317-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000125
AC:
3
AN:
239814
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129588
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000896
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1455880
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
723390
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000684
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 14, 2021The c.47C>T (p.A16V) alteration is located in exon 4 (coding exon 2) of the RNF4 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). 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
0.095
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.36
Cadd
Benign
22
Dann
Uncertain
1.0
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.79
T;.;T;T;T;T;.;.;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.16
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.79
T
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.1
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.087
Sift
Uncertain
0.012
D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.038
D;T;D;T;D;D;D;T;T;D
Polyphen
0.23, 0.81
.;B;.;.;.;P;.;B;B;.
Vest4
0.28, 0.31, 0.31, 0.29
MutPred
0.34
Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP
0.63
MPC
0.49
ClinPred
0.62
D
GERP RS
5.7
Varity_R
0.089
gMVP
0.16

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.

Other links and lift over

dbSNP: rs753448501; hg19: chr4-2498771; API