dbSNP rs751589349: RNF125:p.Pro31Arg (chr18-32018955-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017831.4(RNF125):c.92C>G(p.Pro31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RNF125
NM_017831.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF125	NM_017831.4 link	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 6	ENST00000217740.4	NP_060301.2	Q96EQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF125	ENST00000217740.4 link	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 6	1	NM_017831.4	ENSP00000217740.3	Q96EQ8
RNF125	ENST00000718283.1 link	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 6			ENSP00000520722.1
RNF125	ENST00000718284.1 link	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 5			ENSP00000520723.1
ENSG00000263917	ENST00000583184.1 link	n.127C>G		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111854

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0088

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.73

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

PhyloP100

2.5

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.8

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.51

MutPred

0.32

Gain of loop (P = 0.0435);

MVP

0.57

MPC

0.77

ClinPred

0.93

GERP RS

5.2

PromoterAI

0.088

Neutral

(source)

Varity_R

0.17

gMVP

0.51

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over