18-32018953-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_017831.4(RNF125):c.90G>A(p.Leu30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,802 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
RNF125
NM_017831.4 synonymous
NM_017831.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.82
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 18-32018953-G-A is Benign according to our data. Variant chr18-32018953-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 726819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 74 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF125 | NM_017831.4 | c.90G>A | p.Leu30= | synonymous_variant | 1/6 | ENST00000217740.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF125 | ENST00000217740.4 | c.90G>A | p.Leu30= | synonymous_variant | 1/6 | 1 | NM_017831.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000486 AC: 74AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000962 AC: 24AN: 249594Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135308
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GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461436Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727068
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GnomAD4 genome AF: 0.000486 AC: 74AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74506
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RNF125-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Tenorio syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at