Variant 18-32018884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_017831.4(RNF125):c.21C>T(p.Thr7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,591,738 control chromosomes in the GnomAD database, including 1,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 185 hom., cov: 33)

Exomes 𝑓: 0.028 ( 1374 hom. )

Consequence

RNF125
NM_017831.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 18-32018884-C-T is Benign according to our data. Variant chr18-32018884-C-T is described in ClinVar as [Benign]. Clinvar id is 1168280.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF125	NM_017831.4 linkuse as main transcript	c.21C>T	p.Thr7=	synonymous_variant	1/6	ENST00000217740.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF125	ENST00000217740.4 linkuse as main transcript	c.21C>T	p.Thr7=	synonymous_variant	1/6	1	NM_017831.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4442

AN:

152136

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0438

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.0309

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0381

AC:

7967

AN:

209002

Hom.:

465

AF XY:

0.0360

AC XY:

4091

AN XY:

113762

show subpopulations

Gnomad AFR exome

AF:

0.0220

Gnomad AMR exome

AF:

0.0470

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0276

AC:

39787

AN:

1439484

Hom.:

1374

Cov.:

AF XY:

0.0273

AC XY:

19518

AN XY:

714376

show subpopulations

Gnomad4 AFR exome

AF:

0.0213

Gnomad4 AMR exome

AF:

0.0462

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0338

GnomAD4 genome

AF:

0.0292

AC:

4447

AN:

152254

Hom.:

185

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0438

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.0173

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0316

Asia WGS

AF:

0.114

AC:

396

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tenorio syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over