Variant chr1-44412422-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018150.4(RNF220):c.325A>G(p.Ile109Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,613,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

RNF220
NM_018150.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Variant links:

Genes affected

RNF220 (HGNC:25552): (ring finger protein 220) Predicted to enable ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RNF220 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.13875365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF220	NM_018150.4 linkuse as main transcript	c.325A>G	p.Ile109Val	missense_variant	2/15	ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7 linkuse as main transcript	c.325A>G	p.Ile109Val	missense_variant	2/15	1	NM_018150.4	ENSP00000354872	P1	Q5VTB9-1
RNF220	ENST00000355387.6 linkuse as main transcript	c.325A>G	p.Ile109Val	missense_variant	2/15	1		ENSP00000347548	P1	Q5VTB9-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251062

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000856

AC:

125

AN:

1460868

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Jun 22, 2021

The c.325A>G (p.I109V) alteration is located in exon 2 (coding exon 1) of the RNF220 gene. This alteration results from a A to G substitution at nucleotide position 325, causing the isoleucine (I) at amino acid position 109 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.019

T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

.;.;D

M_CAP

Benign

0.0011

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.67

P;P;P

Vest4

0.44

MVP

0.28

MPC

0.64

ClinPred

0.14

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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