Variant 17-8393250-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001146684.3(RNF222):c.212G>T(p.Ser71Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,551,108 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

RNF222
NM_001146684.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30886036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF222	NM_001146684.3 linkuse as main transcript	c.212G>T	p.Ser71Ile	missense_variant	3/3	ENST00000399398.3	NP_001140156.1	A6NCQ9
RNF222	XM_011523978.4 linkuse as main transcript	c.212G>T	p.Ser71Ile	missense_variant	3/3		XP_011522280.1	A6NCQ9
RNF222	XM_011523980.4 linkuse as main transcript	c.212G>T	p.Ser71Ile	missense_variant	2/2		XP_011522282.1	A6NCQ9
RNF222	XM_011523981.4 linkuse as main transcript	c.212G>T	p.Ser71Ile	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.212G>T	p.Ser71Ile	missense_variant	3/3	5	NM_001146684.3	ENSP00000382330.1		A6NCQ9
RNF222	ENST00000344001.3 linkuse as main transcript	c.212G>T	p.Ser71Ile	missense_variant	1/1	6		ENSP00000343799.3		A6NCQ9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000652

AC:

AN:

153296

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81602

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1398912

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

689986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.0000222

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

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

Jan 17, 2024

The c.212G>T (p.S71I) alteration is located in exon 3 (coding exon 1) of the RNF222 gene. This alteration results from a G to T substitution at nucleotide position 212, causing the serine (S) at amino acid position 71 to be replaced by an isoleucine (I). 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

0.58

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.59

T;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.99

D;D

Vest4

0.33

MutPred

0.48

Loss of disorder (P = 0.013);Loss of disorder (P = 0.013);

MVP

0.26

ClinPred

0.95

GERP RS

3.4

Varity_R

0.56

gMVP

0.52

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