11-117246854-A-G

Variant summary

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

The NM_207343.4(RNF214):ā€‹c.865A>Gā€‹(p.Thr289Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RNF214
NM_207343.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04
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=0.07235831).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF214NM_207343.4 linkuse as main transcriptc.865A>G p.Thr289Ala missense_variant 6/15 ENST00000300650.9
RNF214NM_001077239.2 linkuse as main transcriptc.865A>G p.Thr289Ala missense_variant 6/15
RNF214NM_001278249.2 linkuse as main transcriptc.400A>G p.Thr134Ala missense_variant 6/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.865A>G p.Thr289Ala missense_variant 6/151 NM_207343.4 P3Q8ND24-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1460664
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726626
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsJan 17, 2024The c.865A>G (p.T289A) alteration is located in exon 6 (coding exon 5) of the RNF214 gene. This alteration results from a A to G substitution at nucleotide position 865, causing the threonine (T) at amino acid position 289 to be replaced by an alanine (A). 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
0.27
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.043
T;.;T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
0.031
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.69
T;T;.;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.072
T;T;T;T
MetaSVM
Uncertain
0.47
D
MutationAssessor
Benign
-0.34
N;.;N;.
MutationTaster
Benign
0.79
D;D;D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.77
N;N;N;N
REVEL
Benign
0.074
Sift
Benign
0.40
T;T;T;T
Sift4G
Benign
0.44
T;T;T;T
Polyphen
0.39
B;.;B;.
Vest4
0.30
MutPred
0.21
Loss of phosphorylation at T289 (P = 0.0074);.;Loss of phosphorylation at T289 (P = 0.0074);.;
MVP
0.043
MPC
0.14
ClinPred
0.73
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.033
gMVP
0.35

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: rs2033238369; hg19: chr11-117117570; API