11-117281378-G-A

Variant summary

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

The NM_207343.4(RNF214):​c.1210G>A​(p.Val404Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,612,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14
Variant links:
Genes affected
RNF214 (HGNC:25335): (ring finger protein 214) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10311979).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF214NM_207343.4 linkuse as main transcriptc.1210G>A p.Val404Ile missense_variant 9/15 ENST00000300650.9
RNF214NM_001077239.2 linkuse as main transcriptc.1210G>A p.Val404Ile missense_variant 9/15
RNF214NM_001278249.2 linkuse as main transcriptc.745G>A p.Val249Ile missense_variant 9/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.1210G>A p.Val404Ile missense_variant 9/151 NM_207343.4 P3Q8ND24-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
30
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:
0.0000120
AC:
3
AN:
249524
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135376
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1460958
Hom.:
0
Cov.:
30
AF XY:
0.0000316
AC XY:
23
AN XY:
726896
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74212
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
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
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 submitterclinical testingAmbry GeneticsSep 27, 2022The c.1210G>A (p.V404I) alteration is located in exon 9 (coding exon 8) of the RNF214 gene. This alteration results from a G to A substitution at nucleotide position 1210, causing the valine (V) at amino acid position 404 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
Benign
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.024
T;.;T;.
Eigen
Benign
0.062
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.80
T;T;.;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.14
N;.;N;.
MutationTaster
Benign
0.54
D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.42
N;N;N;N
REVEL
Benign
0.054
Sift
Benign
0.11
T;T;T;T
Sift4G
Benign
0.44
T;T;T;T
Polyphen
0.10
B;.;B;.
Vest4
0.12
MutPred
0.37
Loss of disorder (P = 0.2163);.;Loss of disorder (P = 0.2163);.;
MVP
0.18
MPC
0.51
ClinPred
0.20
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.045
gMVP
0.59

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: rs751012034; hg19: chr11-117152094; API