17-8393173-C-T

Variant summary

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

The NM_001146684.3(RNF222):​c.289G>A​(p.Val97Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,397,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: 0.000021 ( 0 hom. )

Consequence

RNF222
NM_001146684.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
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]

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=0.052808195).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF222NM_001146684.3 linkc.289G>A p.Val97Met missense_variant Exon 3 of 3 ENST00000399398.3 NP_001140156.1 A6NCQ9
RNF222XM_011523978.4 linkc.289G>A p.Val97Met missense_variant Exon 3 of 3 XP_011522280.1 A6NCQ9
RNF222XM_011523980.4 linkc.289G>A p.Val97Met missense_variant Exon 2 of 2 XP_011522282.1 A6NCQ9
RNF222XM_011523981.4 linkc.289G>A p.Val97Met missense_variant Exon 2 of 2 XP_011522283.1 A6NCQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF222ENST00000399398.3 linkc.289G>A p.Val97Met missense_variant Exon 3 of 3 5 NM_001146684.3 ENSP00000382330.1 A6NCQ9
RNF222ENST00000344001.3 linkc.289G>A p.Val97Met missense_variant Exon 1 of 1 6 ENSP00000343799.3 A6NCQ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000675
AC:
1
AN:
148212
Hom.:
0
AF XY:
0.0000126
AC XY:
1
AN XY:
79558
show subpopulations
Gnomad AFR exome
AF:
0.000141
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000207
AC:
29
AN:
1397794
Hom.:
0
Cov.:
34
AF XY:
0.0000218
AC XY:
15
AN XY:
689438
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000232
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289G>A (p.V97M) alteration is located in exon 3 (coding exon 1) of the RNF222 gene. This alteration results from a G to A substitution at nucleotide position 289, causing the valine (V) at amino acid position 97 to be replaced by a methionine (M). 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
0.11
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
9.0
DANN
Benign
0.62
DEOGEN2
Benign
0.00077
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.49
T;.
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.19
N;N
REVEL
Benign
0.019
Sift
Benign
0.29
T;T
Sift4G
Benign
0.28
T;T
Polyphen
0.43
B;B
Vest4
0.081
MutPred
0.23
Gain of solvent accessibility (P = 0.0273);Gain of solvent accessibility (P = 0.0273);
MVP
0.014
ClinPred
0.35
T
GERP RS
-2.1
Varity_R
0.038
gMVP
0.16

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.

Other links and lift over

dbSNP: rs1567711737; hg19: chr17-8296491; API