rs144268137

Variant names:

• chr18-32042247-A-G
• rs144268137
• NM_017831.4:c.387A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017831.4(RNF125):​c.387A>G​(p.Leu129Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,042 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (11 hom.)
• Consequence: RNF125 NM_017831.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58
• Publications: 1 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, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000263917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 18-32042247-A-G is Benign according to our data. Variant chr18-32042247-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BS2: High AC in GnomAd4 at 389 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.387A>G	p.Leu129Leu	synonymous	Exon 3 of 6	NP_060301.2
	RNF125	NM_001436860.1		c.387A>G	p.Leu129Leu	synonymous	Exon 3 of 6	NP_001423789.1	A0ABB0MVB6
	RNF125	NM_001436861.1		c.387A>G	p.Leu129Leu	synonymous	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.387A>G	p.Leu129Leu	synonymous	Exon 3 of 6	ENSP00000217740.3	Q96EQ8
	RNF125	ENST00000718283.1		c.387A>G	p.Leu129Leu	synonymous	Exon 3 of 6	ENSP00000520722.1	A0ABB0MVB6
	RNF125	ENST00000909753.1		c.387A>G	p.Leu129Leu	synonymous	Exon 3 of 5	ENSP00000579812.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00254 AC: 637 AN: 250954 AF XY: 0.00246

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00224 AC: 3277 AN: 1460714 Hom.: 11 Cov.: 29 AF XY: 0.00213 AC XY: 1546 AN XY: 726704

African (AFR) AF: 0.000149 AC: 5 AN: 33456

American (AMR) AF: 0.000694 AC: 31 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39646

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86150

European-Finnish (FIN) AF: 0.0178 AC: 950 AN: 53402

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5670

European-Non Finnish (NFE) AF: 0.00193 AC: 2148 AN: 1111256

Other (OTH) AF: 0.00187 AC: 113 AN: 60330

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74494

African (AFR) AF: 0.000216 AC: 9 AN: 41588

American (AMR) AF: 0.000654 AC: 10 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00219 AC: 149 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00168 Hom.: 1

Bravo AF: 0.000986

EpiCase AF: 0.00115

EpiControl AF: 0.00225

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Tenorio syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.36
DANN	Benign	0.77
PhyloP100		-1.6
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs144268137; hg19: chr18-29622210;