18-32065967-A-C

Variant names:

• chr18-32065967-A-C
• NM_017831.4:c.570A>C
• RNF125 p.Arg190Ser

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017831.4(RNF125):​c.570A>C​(p.Arg190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF125 NM_017831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000263917 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• 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.570A>C	p.Arg190Ser	missense	Exon 5 of 6	NP_060301.2
	RNF125	NM_001436860.1		c.570A>C	p.Arg190Ser	missense	Exon 5 of 6	NP_001423789.1	A0ABB0MVB6
	RNF125	NM_001436861.1		c.504+20235A>C		intron	N/A	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.570A>C	p.Arg190Ser	missense	Exon 5 of 6	ENSP00000217740.3	Q96EQ8
	RNF125	ENST00000718283.1		c.570A>C	p.Arg190Ser	missense	Exon 5 of 6	ENSP00000520722.1	A0ABB0MVB6
	RNF125	ENST00000909753.1		c.505-2331A>C		intron	N/A	ENSP00000579812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.21	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.010	D
Varity_R		0.24
gMVP		0.79
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr18-29645930;

COSMIC: COSV54185568;