Variant 17-8392830-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001146684.3(RNF222):c.632C>T(p.Pro211Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,532,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RNF222
NM_001146684.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.74

Variant links:

Genes affected

RNF222 (HGNC:34517): (ring finger protein 222) Predicted to enable metal ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF222 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF222	NM_001146684.3 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	3/3	ENST00000399398.3	NP_001140156.1	A6NCQ9
RNF222	XM_011523978.4 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	3/3		XP_011522280.1	A6NCQ9
RNF222	XM_011523980.4 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	2/2		XP_011522282.1	A6NCQ9
RNF222	XM_011523981.4 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	2/2		XP_011522283.1	A6NCQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF222	ENST00000399398.3 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	3/3	5	NM_001146684.3	ENSP00000382330.1		A6NCQ9
RNF222	ENST00000344001.3 linkuse as main transcript	c.632C>T	p.Pro211Leu	missense_variant	1/1	6		ENSP00000343799.3		A6NCQ9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000116

AC:

AN:

129856

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

70906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000534

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:

0.0000407

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1380572

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

681284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000449

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:

0.00000835

Gnomad4 OTH exome

AF:

0.0000694

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

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:

0.0000712

Hom.:

Bravo

AF:

0.0000680

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 02, 2023

The c.632C>T (p.P211L) alteration is located in exon 3 (coding exon 1) of the RNF222 gene. This alteration results from a C to T substitution at nucleotide position 632, causing the proline (P) at amino acid position 211 to be replaced by a leucine (L). 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

Pathogenic

0.95

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

T;.

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.83

N;N

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.64

MutPred

0.34

Loss of catalytic residue at P211 (P = 0.0236);Loss of catalytic residue at P211 (P = 0.0236);

MVP

0.39

ClinPred

0.21

GERP RS

4.8

Varity_R

0.64

gMVP

0.90

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