Variant 18-32018953-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_017831.4(RNF125):c.90G>A(p.Leu30Leu) 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 Benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

RNF125
NM_017831.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.82

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]

RNF125 links:

ENSG00000263917 (HGNC:):

ENSG00000263917 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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 [Benign]. Clinvar id is 726819.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF125	NM_017831.4 linkuse as main transcript	c.90G>A	p.Leu30Leu	synonymous_variant	1/6	ENST00000217740.4	NP_060301.2	Q96EQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF125	ENST00000217740.4 linkuse as main transcript	c.90G>A	p.Leu30Leu	synonymous_variant	1/6	1	NM_017831.4	ENSP00000217740.3		Q96EQ8
ENSG00000263917	ENST00000583184.1 linkuse as main transcript	n.125G>A		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000962

AC:

AN:

249594

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.00143

Gnomad AMR exome

AF:

0.0000291

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:

0.0000465

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000486

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000552

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RNF125-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

Labcorp Genetics (formerly Invitae), Labcorp

May 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.96

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over