11-117238920-C-G

Variant summary

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

The NM_207343.4(RNF214):ā€‹c.427C>Gā€‹(p.Gln143Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000036 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
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 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=0.0350309).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF214NM_207343.4 linkuse as main transcriptc.427C>G p.Gln143Glu missense_variant 3/15 ENST00000300650.9 NP_997226.2
RNF214NM_001077239.2 linkuse as main transcriptc.427C>G p.Gln143Glu missense_variant 3/15 NP_001070707.1
RNF214NM_001278249.2 linkuse as main transcriptc.153+274C>G intron_variant NP_001265178.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.427C>G p.Gln143Glu missense_variant 3/151 NM_207343.4 ENSP00000300650 P3Q8ND24-1

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000652
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:
0.0000294
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000521
AC:
13
AN:
249512
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135382
show subpopulations
Gnomad AFR exome
AF:
0.000646
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:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461876
Hom.:
0
Cov.:
33
AF XY:
0.0000303
AC XY:
22
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.0000671
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:
0.0000144
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.000652
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:
0.0000294
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000397
Hom.:
0
Bravo
AF:
0.000215
ESP6500AA
AF:
0.000254
AC:
1
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000744
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsOct 12, 2022The c.427C>G (p.Q143E) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a C to G substitution at nucleotide position 427, causing the glutamine (Q) at amino acid position 143 to be replaced by a glutamic acid (E). 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
0.065
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.021
T;T;T
Eigen
Benign
-0.17
Eigen_PC
Benign
0.0059
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.70
T;T;.
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.035
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
.;N;N
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.91
N;N;N
REVEL
Benign
0.053
Sift
Benign
0.098
T;T;T
Sift4G
Pathogenic
0.0
D;T;T
Polyphen
0.0
.;B;B
Vest4
0.24, 0.23
MVP
0.082
MPC
0.048
ClinPred
0.022
T
GERP RS
4.8
Varity_R
0.17
gMVP
0.097

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs199938335; hg19: chr11-117109636; API