18-32042247-A-G

Position:

• chr18-32042247-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017831.4(RNF125):​c.387A>G​(p.Leu129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,042 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (11 hom.)
• Consequence: RNF125 NM_017831.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 18-32042247-A-G is Benign according to our data. Variant chr18-32042247-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 475384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BS2: High AC in GnomAd4 at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF125	NM_017831.4	c.387A>G	p.Leu129=	synonymous_variant	3/6	ENST00000217740.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF125	ENST00000217740.4	c.387A>G	p.Leu129=	synonymous_variant	3/6	1	NM_017831.4	P1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00254 AC: 637 AN: 250954 Hom.: 3 AF XY: 0.00246 AC XY: 334 AN XY: 135626

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00224 AC: 3277 AN: 1460714 Hom.: 11 Cov.: 29 AF XY: 0.00213 AC XY: 1546 AN XY: 726704

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000694

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.00193

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74494

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.00219

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00168 Hom.: 1

Bravo AF: 0.000986

EpiCase AF: 0.00115

EpiControl AF: 0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tenorio syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

RNF125: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.36
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs144268137; hg19: chr18-29622210;