11-117238936-A-G

Variant summary

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

The NM_207343.4(RNF214):​c.443A>G​(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNF214
NM_207343.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954
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=0.0564591).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF214NM_207343.4 linkuse as main transcriptc.443A>G p.Asn148Ser missense_variant 3/15 ENST00000300650.9 NP_997226.2
RNF214NM_001077239.2 linkuse as main transcriptc.443A>G p.Asn148Ser missense_variant 3/15 NP_001070707.1
RNF214NM_001278249.2 linkuse as main transcriptc.153+290A>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.443A>G p.Asn148Ser missense_variant 3/151 NM_207343.4 ENSP00000300650 P3Q8ND24-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

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 GeneticsJul 05, 2023The c.443A>G (p.N148S) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a A to G substitution at nucleotide position 443, causing the asparagine (N) at amino acid position 148 to be replaced by a serine (S). 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
0.084
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.74
T;.
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.51
N;N
REVEL
Benign
0.15
Sift
Benign
0.064
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.0
B;B
Vest4
0.16
MutPred
0.059
Gain of phosphorylation at N148 (P = 0.014);Gain of phosphorylation at N148 (P = 0.014);
MVP
0.068
MPC
0.039
ClinPred
0.091
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.074
gMVP
0.077

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: rs2032993380; hg19: chr11-117109652; API