chr18-32018888-AGCG-A

Position:

• chr18-32018888-AGCG-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_017831.4(RNF125):​c.28_30del​(p.Gly10del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,594,980 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: RNF125 NM_017831.4 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017831.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 18-32018888-AGCG-A is Benign according to our data. Variant chr18-32018888-AGCG-A is described in ClinVar as [Benign]. Clinvar id is 707497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF125	NM_017831.4	c.28_30del	p.Gly10del	inframe_deletion	1/6	ENST00000217740.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF125	ENST00000217740.4	c.28_30del	p.Gly10del	inframe_deletion	1/6	1	NM_017831.4	P1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000421 AC: 90 AN: 213658 Hom.: 2 AF XY: 0.000335 AC XY: 39 AN XY: 116434

Gnomad AFR exome AF: 0.00691

Gnomad AMR exome AF: 0.0000663

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000106

Gnomad OTH exome AF: 0.000187

GnomAD4 exome AF: 0.000187 AC: 270 AN: 1442642 Hom.: 0 AF XY: 0.000159 AC XY: 114 AN XY: 716238

Gnomad4 AFR exome AF: 0.00688

Gnomad4 AMR exome AF: 0.0000242

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000218

Gnomad4 OTH exome AF: 0.000268

GnomAD4 genome AF: 0.00161 AC: 246 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74500

Gnomad4 AFR AF: 0.00568

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000866 Hom.: 0

Bravo AF: 0.00177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Tenorio syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs753146462; hg19: chr18-29598851;