2-218664465-G-C

Position:

• chr2-218664465-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022453.3(RNF25):​c.872C>G​(p.Ala291Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF25 NM_022453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

Genes affected

RNF25 (HGNC:14662): (ring finger protein 25) The protein encoded by this gene contains a RING finger motif. The mouse counterpart of this protein has been shown to interact with Rela, the p65 subunit of NF-kappaB (NFKB), and modulate NFKB-mediated transcription activity. The mouse protein also binds ubiquitin-conjugating enzymes (E2s) and is a substrate for E2-dependent ubiquitination. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08104429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF25	NM_022453.3	c.872C>G	p.Ala291Gly	missense_variant	10/10	ENST00000295704.7	NP_071898.2
RNF25	XM_017004695.3	c.536C>G	p.Ala179Gly	missense_variant	10/10		XP_016860184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF25	ENST00000295704.7	c.872C>G	p.Ala291Gly	missense_variant	10/10	1	NM_022453.3	ENSP00000295704	P1
RNF25	ENST00000473034.5	n.1234C>G		non_coding_transcript_exon_variant	8/8	2
RNF25	ENST00000474339.1	n.234C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.872C>G (p.A291G) alteration is located in exon 10 (coding exon 10) of the RNF25 gene. This alteration results from a C to G substitution at nucleotide position 872, causing the alanine (A) at amino acid position 291 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.86	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.060
Sift	Benign	0.17	T
Sift4G	Benign	0.083	T
Polyphen		0.38	B
Vest4		0.059
MutPred		0.050		Gain of catalytic residue at P287 (P = 0.1189);
MVP		0.27
MPC		0.20
ClinPred		0.21	T
GERP RS		4.5
Varity_R		0.042
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219529188;