chr18-32045716-C-A

Variant names:

• chr18-32045716-C-A
• rs373764886
• NM_017831.4:c.488C>A

Variant summary

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

The NM_017831.4(RNF125):​c.488C>A​(p.Ser163*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S163S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 27)
• Consequence: RNF125 NM_017831.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 4 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ENSG00000263917 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF125	NM_017831.4	c.488C>A	p.Ser163*	stop_gained	Exon 4 of 6	ENST00000217740.4	NP_060301.2
RNF125	NM_001436860.1	c.488C>A	p.Ser163*	stop_gained	Exon 4 of 6		NP_001423789.1
RNF125	NM_001436861.1	c.488C>A	p.Ser163*	stop_gained	Exon 4 of 5		NP_001423790.1
RNF125	XM_011526046.4	c.488C>A	p.Ser163*	stop_gained	Exon 4 of 5		XP_011524348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF125	ENST00000217740.4	c.488C>A	p.Ser163*	stop_gained	Exon 4 of 6	1	NM_017831.4	ENSP00000217740.3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 27

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.85	D
PhyloP100		2.9
Vest4		0.32
GERP RS		5.8
Mutation Taster		=52/148	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs373764886; hg19: chr18-29625679;