18-32065967-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017831.4(RNF125):c.570A>T(p.Arg190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,613,084 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 38 hom. )

Consequence

RNF125
NM_017831.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.41

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Tenorio syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

RNF125 links:

ENSG00000263917 (HGNC:):

ENSG00000263917 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010693252).

BP6

Variant 18-32065967-A-T is Benign according to our data. Variant chr18-32065967-A-T is described in ClinVar as Benign. ClinVar VariationId is 475385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1565/152296) while in subpopulation AFR AF = 0.0294 (1220/41562). AF 95% confidence interval is 0.028. There are 10 homozygotes in GnomAd4. There are 761 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF125	NM_017831.4 link	c.570A>T	p.Arg190Ser	missense_variant	Exon 5 of 6	ENST00000217740.4	NP_060301.2	Q96EQ8
RNF125	NM_001436860.1 link	c.570A>T	p.Arg190Ser	missense_variant	Exon 5 of 6		NP_001423789.1
RNF125	NM_001436861.1 link	c.504+20235A>T		intron_variant	Intron 4 of 4		NP_001423790.1
RNF125	XM_011526046.4 link	c.505-2331A>T		intron_variant	Intron 4 of 4		XP_011524348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF125	ENST00000217740.4 link	c.570A>T	p.Arg190Ser	missense_variant	Exon 5 of 6	1	NM_017831.4	ENSP00000217740.3		Q96EQ8

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1556

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00435

AC:

1094

AN:

251422

AF XY:

0.00400

show subpopulations

Gnomad AFR exome

AF:

0.0311

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00283

AC:

4139

AN:

1460788

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2067

AN XY:

726784

show subpopulations

African (AFR)

AF:

0.0310

AC:

1036

AN:

33458

American (AMR)

AF:

0.00532

AC:

238

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00524

AC:

137

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00334

AC:

288

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00919

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00187

AC:

2080

AN:

1111038

Other (OTH)

AF:

0.00509

AC:

307

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

178

357

535

714

892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0103

AC:

1565

AN:

152296

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

761

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0294

AC:

1220

AN:

41562

American (AMR)

AF:

0.00988

AC:

151

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00169

AC:

115

AN:

68032

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0281

AC:

124

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00489

AC:

594

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00333

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Tenorio syndrome

Benign:1

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.71

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.3

PhyloP100

2.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.21

REVEL

Uncertain

0.40

Sift

Uncertain

0.013

Sift4G

Uncertain

0.010

Polyphen

0.98

Vest4

0.74

MutPred

0.37

Gain of helix (P = 0.0325);

MVP

0.94

MPC

1.1

ClinPred

0.014

GERP RS

3.5

Varity_R

0.24

gMVP

0.79

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over