dbSNP rs782385808: RNF34:p.Arg177Ser (chr12-121417807-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025126.4(RNF34):c.529C>A(p.Arg177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R177H) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

RNF34
NM_025126.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.16

Publications

2 publications found

Variant links:

Genes affected

RNF34 (HGNC:17297): (ring finger protein 34) The protein encoded by this gene contains a RINF finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein interacts with DNAJA3/hTid-1, which is a DnaJ protein reported to function as a modulator of apoptosis. Overexpression of this gene in Hela cells was shown to confer the resistance to TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of this protein. This protein can be cleaved by caspase-3 during the induction of apoptosis. This protein also targets p53 and phospho-p53 for degradation. Alternatively splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

RNF34 links:

KDM2B (HGNC:13610): (lysine demethylase 2B) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

KDM2B Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

KDM2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10076329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025126.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF34	NM_025126.4	MANE Select	c.529C>A	p.Arg177Ser	missense	Exon 3 of 6	NP_079402.2
RNF34	NM_001394208.1		c.532C>A	p.Arg178Ser	missense	Exon 5 of 8	NP_001381137.1	Q969K3-2
RNF34	NM_194271.3		c.532C>A	p.Arg178Ser	missense	Exon 4 of 7	NP_919247.1	Q969K3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF34	ENST00000361234.10	TSL:1 MANE Select	c.529C>A	p.Arg177Ser	missense	Exon 3 of 6	ENSP00000355137.5	Q969K3-1
RNF34	ENST00000392464.3	TSL:5	c.529C>A	p.Arg177Ser	missense	Exon 3 of 7	ENSP00000376257.2	H7BYJ1
RNF34	ENST00000392465.7	TSL:5	c.532C>A	p.Arg178Ser	missense	Exon 4 of 7	ENSP00000376258.3	Q969K3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.0053

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

PhyloP100

2.2

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.13

REVEL

Benign

0.074

Sift

Benign

0.25

Sift4G

Benign

0.72

Polyphen

0.0020

Vest4

0.31

MutPred

0.32

Gain of catalytic residue at F179 (P = 9e-04)

MVP

0.40

MPC

0.55

ClinPred

0.36

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.34

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over