NM_025126.4:c.705A>G

Variant names:

• chr12-121420313-A-G
• rs61751317
• NM_025126.4:c.705A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_025126.4(RNF34):​c.705A>G​(p.Glu235Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF34 NM_025126.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF34	NM_025126.4	MANE Select	c.705A>G	p.Glu235Glu	synonymous	Exon 4 of 6	NP_079402.2
	RNF34	NM_001394208.1		c.708A>G	p.Glu236Glu	synonymous	Exon 6 of 8	NP_001381137.1	Q969K3-2
	RNF34	NM_194271.3		c.708A>G	p.Glu236Glu	synonymous	Exon 5 of 7	NP_919247.1	Q969K3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF34	ENST00000361234.10	TSL:1 MANE Select	c.705A>G	p.Glu235Glu	synonymous	Exon 4 of 6	ENSP00000355137.5	Q969K3-1
	RNF34	ENST00000392464.3	TSL:5	c.705A>G	p.Glu235Glu	synonymous	Exon 4 of 7	ENSP00000376257.2	H7BYJ1
	RNF34	ENST00000392465.7	TSL:5	c.708A>G	p.Glu236Glu	synonymous	Exon 5 of 7	ENSP00000376258.3	Q969K3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424592 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 706238

African (AFR) AF: 0.00 AC: 0 AN: 32058

American (AMR) AF: 0.00 AC: 0 AN: 39336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 37042

South Asian (SAS) AF: 0.00 AC: 0 AN: 82054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1092116

Other (OTH) AF: 0.00 AC: 0 AN: 59098

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.14
PhyloP100		-3.8

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

Other links and lift over

dbSNP: rs61751317; hg19: chr12-121858116;