rs979916916
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The ENST00000217740.4(RNF125):āc.122T>Cā(p.Leu41Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000046 ( 0 hom. )
Consequence
RNF125
ENST00000217740.4 missense
ENST00000217740.4 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 3.93
Genes affected
RNF125 (HGNC:21150): (ring finger protein 125) This gene encodes a novel E3 ubiquitin ligase that contains a RING finger domain in the N-terminus and three zinc-binding and one ubiquitin-interacting motif in the C-terminus. As a result of myristoylation, this protein associates with membranes and is primarily localized to intracellular membrane systems. The encoded protein may function as a positive regulator in the T-cell receptor signaling pathway. [provided by RefSeq, Mar 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918
BP6
Variant 18-32018985-T-C is Benign according to our data. Variant chr18-32018985-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436546.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAdExome4 at 67 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF125 | NM_017831.4 | c.122T>C | p.Leu41Pro | missense_variant | 1/6 | ENST00000217740.4 | NP_060301.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF125 | ENST00000217740.4 | c.122T>C | p.Leu41Pro | missense_variant | 1/6 | 1 | NM_017831.4 | ENSP00000217740 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152124
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: 0.0000120 AC: 3AN: 250288Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135480
GnomAD3 exomes
AF:
AC:
3
AN:
250288
Hom.:
AF XY:
AC XY:
2
AN XY:
135480
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: 0.0000458 AC: 67AN: 1461408Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727028
GnomAD4 exome
AF:
AC:
67
AN:
1461408
Hom.:
Cov.:
31
AF XY:
AC XY:
39
AN XY:
727028
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: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74294
GnomAD4 genome
AF:
AC:
3
AN:
152124
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74294
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
RNF125-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 13, 2023 | The RNF125 c.122T>C variant is predicted to result in the amino acid substitution p.Leu41Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0031% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-29598948-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 16, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0218);
MVP
MPC
ClinPred
D
GERP RS
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