chr12-121420683-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025126.4(RNF34):c.833G>A(p.Arg278Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,916 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 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
RNF34
NM_025126.4 missense
NM_025126.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.42
Genes affected
RNF34 (HGNC:17297): (ring finger protein 34) The protein encoded by this gene contains a RINF finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein interacts with DNAJA3/hTid-1, which is a DnaJ protein reported to function as a modulator of apoptosis. Overexpression of this gene in Hela cells was shown to confer the resistance to TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of this protein. This protein can be cleaved by caspase-3 during the induction of apoptosis. This protein also targets p53 and phospho-p53 for degradation. Alternatively splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]
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=0.288207).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF34 | NM_025126.4 | c.833G>A | p.Arg278Gln | missense_variant | 5/6 | ENST00000361234.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF34 | ENST00000361234.10 | c.833G>A | p.Arg278Gln | missense_variant | 5/6 | 1 | NM_025126.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152132Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
9
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251476Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135914
GnomAD3 exomes
AF:
AC:
8
AN:
251476
Hom.:
AF XY:
AC XY:
4
AN XY:
135914
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727210
GnomAD4 exome
AF:
AC:
34
AN:
1461784
Hom.:
Cov.:
31
AF XY:
AC XY:
17
AN XY:
727210
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74298
GnomAD4 genome
?
AF:
AC:
9
AN:
152132
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ExAC
?
AF:
AC:
1
Asia WGS
AF:
AC:
2
AN:
3478
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 submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.836G>A (p.R279Q) alteration is located in exon 6 (coding exon 5) of the RNF34 gene. This alteration results from a G to A substitution at nucleotide position 836, causing the arginine (R) at amino acid position 279 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Benign
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;T;D;D
Polyphen
D;.;D;.
Vest4
MutPred
Gain of catalytic residue at F280 (P = 9e-04);.;.;Gain of catalytic residue at F280 (P = 9e-04);
MVP
MPC
1.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at