18-32037292-T-G

Variant names:

• chr18-32037292-T-G
• rs9947278
• NM_017831.4:c.318+23T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017831.4(RNF125):​c.318+23T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,486,020 control chromosomes in the GnomAD database, including 370,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39714 hom., cov: 26)
  • Exomes 𝑓: 0.70 (331042 hom.)
• Consequence: RNF125 NM_017831.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.321
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-32037292-T-G is Benign according to our data. Variant chr18-32037292-T-G is described in ClinVar as [Benign]. Clinvar id is 1327959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF125	NM_017831.4	c.318+23T>G		intron_variant	Intron 2 of 5	ENST00000217740.4	NP_060301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF125	ENST00000217740.4	c.318+23T>G		intron_variant	Intron 2 of 5	1	NM_017831.4	ENSP00000217740.3

Frequencies

GnomAD3 genomes AF: 0.721 AC: 108488 AN: 150382 Hom.: 39650 Cov.: 26

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.670

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.685 AC: 117153 AN: 171132 AF XY: 0.686

Gnomad AFR exome AF: 0.833

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.408

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.713

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.701 AC: 936841 AN: 1335522 Hom.: 331042 Cov.: 21 AF XY: 0.701 AC XY: 462684 AN XY: 659904

African (AFR) AF: 0.836 AC: 22683 AN: 27120

American (AMR) AF: 0.620 AC: 15109 AN: 24352

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 15508 AN: 22122

East Asian (EAS) AF: 0.443 AC: 14446 AN: 32630

South Asian (SAS) AF: 0.676 AC: 47151 AN: 69760

European-Finnish (FIN) AF: 0.667 AC: 34527 AN: 51802

Middle Eastern (MID) AF: 0.734 AC: 3967 AN: 5404

European-Non Finnish (NFE) AF: 0.711 AC: 744753 AN: 1047200

Other (OTH) AF: 0.702 AC: 38697 AN: 55132

GnomAD4 genome AF: 0.722 AC: 108613 AN: 150498 Hom.: 39714 Cov.: 26 AF XY: 0.716 AC XY: 52474 AN XY: 73280

African (AFR) AF: 0.826 AC: 33807 AN: 40922

American (AMR) AF: 0.651 AC: 9759 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2449 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2157 AN: 5130

South Asian (SAS) AF: 0.673 AC: 3201 AN: 4754

European-Finnish (FIN) AF: 0.657 AC: 6662 AN: 10138

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.714 AC: 48408 AN: 67822

Other (OTH) AF: 0.712 AC: 1483 AN: 2082

Alfa AF: 0.715 Hom.: 75490

Bravo AF: 0.725

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tenorio syndrome Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.63
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9947278; hg19: chr18-29617255; COSMIC: COSV54183935; COSMIC: COSV54183935;