rs786201014

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_017831.4(RNF125):​c.336G>A​(p.Met112Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

RNF125
NM_017831.4 missense

Scores

4
10
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.85
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 18-32042196-G-A is Pathogenic according to our data. Variant chr18-32042196-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 183420.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-32042196-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF125NM_017831.4 linkuse as main transcriptc.336G>A p.Met112Ile missense_variant 3/6 ENST00000217740.4 NP_060301.2 Q96EQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF125ENST00000217740.4 linkuse as main transcriptc.336G>A p.Met112Ile missense_variant 3/61 NM_017831.4 ENSP00000217740.3 Q96EQ8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Tenorio syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.085
T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.72
T
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Uncertain
0.027
D
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.0
D
REVEL
Pathogenic
0.82
Sift
Benign
0.24
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.85
P
Vest4
0.84
MutPred
0.52
Loss of solvent accessibility (P = 0.0015);
MVP
0.92
MPC
0.45
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.63
gMVP
0.59

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: rs786201014; hg19: chr18-29622159; API