Variant chr2-218664318-G-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.1019C>A(p.Pro340His) variant causes a missense change. The variant allele was found at a frequency of 0.0000682 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RNF25
ENST00000295704.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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:

Genome browser will be placed here

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=0.011971295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF25	NM_022453.3 linkuse as main transcript	c.1019C>A	p.Pro340His	missense_variant	10/10	ENST00000295704.7	NP_071898.2	Q96BH1
RNF25	XM_017004695.3 linkuse as main transcript	c.683C>A	p.Pro228His	missense_variant	10/10		XP_016860184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF25	ENST00000295704.7 linkuse as main transcript	c.1019C>A	p.Pro340His	missense_variant	10/10	1	NM_022453.3	ENSP00000295704.2	Q96BH1
RNF25	ENST00000473034.5 linkuse as main transcript	n.1381C>A		non_coding_transcript_exon_variant	8/8	2
RNF25	ENST00000474339.1 linkuse as main transcript	n.381C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251250

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000401

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000595

Hom.:

Bravo

AF:

0.000453

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 03, 2022

The c.1019C>A (p.P340H) alteration is located in exon 10 (coding exon 10) of the RNF25 gene. This alteration results from a C to A substitution at nucleotide position 1019, causing the proline (P) at amino acid position 340 to be replaced by a histidine (H). 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

0.093

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

0.17

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

M_CAP

Benign

0.0079

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.56

REVEL

Benign

0.058

Sift

Benign

0.080

Sift4G

Benign

0.47

Polyphen

0.88

Vest4

0.29

MVP

0.25

MPC

0.66

ClinPred

0.046

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.051

gMVP

0.11

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