rs766520562

Variant names:

• chr18-32018910-C-G
• rs766520562
• NM_017831.4:c.47C>G
• RNF125 p.Ser16Cys

Your query was ambiguous. Multiple possible variants found:

• chr18-32018910-C-G
• chr18-32018910-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_017831.4(RNF125):​c.47C>G​(p.Ser16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,607,556 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: RNF125 NM_017831.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Tenorio syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000263917 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18297139).
• BS2: High AC in GnomAdExome4 at 86 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF125	NM_017831.4	MANE Select	c.47C>G	p.Ser16Cys	missense	Exon 1 of 6	NP_060301.2
	RNF125	NM_001436860.1		c.47C>G	p.Ser16Cys	missense	Exon 1 of 6	NP_001423789.1	A0ABB0MVB6
	RNF125	NM_001436861.1		c.47C>G	p.Ser16Cys	missense	Exon 1 of 5	NP_001423790.1	A0ABB0MVB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF125	ENST00000217740.4	TSL:1 MANE Select	c.47C>G	p.Ser16Cys	missense	Exon 1 of 6	ENSP00000217740.3	Q96EQ8
	RNF125	ENST00000718283.1		c.47C>G	p.Ser16Cys	missense	Exon 1 of 6	ENSP00000520722.1	A0ABB0MVB6
	RNF125	ENST00000909753.1		c.47C>G	p.Ser16Cys	missense	Exon 1 of 5	ENSP00000579812.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000383 AC: 9 AN: 235232 AF XY: 0.0000468

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000853

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000591 AC: 86 AN: 1455320 Hom.: 0 Cov.: 31 AF XY: 0.0000677 AC XY: 49 AN XY: 723548

African (AFR) AF: 0.0000300 AC: 1 AN: 33304

American (AMR) AF: 0.0000229 AC: 1 AN: 43590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 85310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52670

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000721 AC: 80 AN: 1109268

Other (OTH) AF: 0.0000499 AC: 3 AN: 60096

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Tenorio syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.32
Sift	Benign	0.031	D
Sift4G	Uncertain	0.023	D
PromoterAI		-0.052	Neutral
Varity_R		0.19
gMVP		0.41
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs766520562;

hg19: chr18-29598873;