18-32042245-CTA-TTG

Variant names:

• chr18-32042245-CTA-TTG
• NM_017831.4:c.385_387delCTAinsTTG
• RNF125 p.130

Variant summary

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

The NM_017831.4(RNF125):​c.385_387delCTAinsTTG​(p.130) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L129L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNF125 NM_017831.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.385_387delCTAinsTTG	p.130	synonymous	N/A	NP_060301.2
	RNF125	NM_001436860.1		c.385_387delCTAinsTTG	p.130	synonymous	N/A	NP_001423789.1	A0ABB0MVB6
	RNF125	NM_001436861.1		c.385_387delCTAinsTTG	p.130	synonymous	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.385_387delCTAinsTTG	p.130	synonymous	N/A	ENSP00000217740.3	Q96EQ8
	RNF125	ENST00000718283.1		c.385_387delCTAinsTTG	p.130	synonymous	N/A	ENSP00000520722.1	A0ABB0MVB6
	RNF125	ENST00000909753.1		c.385_387delCTAinsTTG	p.130	synonymous	N/A	ENSP00000579812.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

Splicing

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: chr18-29622208;