Variant chr2-218664821-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000295704.7(RNF25):c.719G>A(p.Arg240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,892 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 33)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

RNF25
ENST00000295704.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.117

Variant links:

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]

RNF25 links:

RNF25 (HGNC:):

RNF25 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039568573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF25	NM_022453.3 linkuse as main transcript	c.719G>A	p.Arg240Gln	missense_variant	9/10	ENST00000295704.7	NP_071898.2	Q96BH1
RNF25	XM_017004695.3 linkuse as main transcript	c.383G>A	p.Arg128Gln	missense_variant	9/10		XP_016860184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF25	ENST00000295704.7 linkuse as main transcript	c.719G>A	p.Arg240Gln	missense_variant	9/10	1	NM_022453.3	ENSP00000295704.2	Q96BH1
RNF25	ENST00000473034.5 linkuse as main transcript	n.1081G>A		non_coding_transcript_exon_variant	7/8	2
RNF25	ENST00000474339.1 linkuse as main transcript	n.81G>A		non_coding_transcript_exon_variant	1/2	2
RNF25	ENST00000463188.5 linkuse as main transcript	n.*6G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251460

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.719G>A (p.R240Q) alteration is located in exon 9 (coding exon 9) of the RNF25 gene. This alteration results from a G to A substitution at nucleotide position 719, causing the arginine (R) at amino acid position 240 to be replaced by a glutamine (Q). 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

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.71

M_CAP

Benign

0.0071

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.50

REVEL

Benign

0.052

Sift

Benign

0.54

Sift4G

Benign

0.68

Polyphen

0.014

Vest4

0.26

MutPred

0.21

Loss of MoRF binding (P = 0.0126);

MVP

0.37

MPC

0.18

ClinPred

0.035

GERP RS

2.9

Varity_R

0.063

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over