RNF125 p.Met112Ile

Variant names:

• chr18-32042196-G-T
• NM_017831.4:c.336G>T
• RNF125 p.Met112Ile

Your query was ambiguous. Multiple possible variants found:

• chr18-32042196-G-T
• chr18-32042196-G-C
• chr18-32042196-G-A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PS1 PM2

The NM_017831.4(RNF125):​c.336G>T​(p.Met112Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNF125 NM_017831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• 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_pathogenic. The variant received 6 ACMG points.

• PS1: Transcript NM_017831.4 (RNF125) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage

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.336G>T	p.Met112Ile	missense	Exon 3 of 6	NP_060301.2
	RNF125	NM_001436860.1		c.336G>T	p.Met112Ile	missense	Exon 3 of 6	NP_001423789.1	A0ABB0MVB6
	RNF125	NM_001436861.1		c.336G>T	p.Met112Ile	missense	Exon 3 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.336G>T	p.Met112Ile	missense	Exon 3 of 6	ENSP00000217740.3	Q96EQ8
	RNF125	ENST00000718283.1		c.336G>T	p.Met112Ile	missense	Exon 3 of 6	ENSP00000520722.1	A0ABB0MVB6
	RNF125	ENST00000909753.1		c.336G>T	p.Met112Ile	missense	Exon 3 of 5	ENSP00000579812.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.027	D
MutationAssessor	Benign	1.8	L
PhyloP100		3.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.80
Sift	Benign	0.24	T
Sift4G	Pathogenic	0.0	D
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

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

Other links and lift over

hg19: chr18-29622159;

COSMIC: COSV54184308;