11-117279941-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207343.4(RNF214):​c.993G>C​(p.Lys331Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNF214
NM_207343.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF214NM_207343.4 linkuse as main transcriptc.993G>C p.Lys331Asn missense_variant 7/15 ENST00000300650.9
RNF214NM_001077239.2 linkuse as main transcriptc.993G>C p.Lys331Asn missense_variant 7/15
RNF214NM_001278249.2 linkuse as main transcriptc.528G>C p.Lys176Asn missense_variant 7/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.993G>C p.Lys331Asn missense_variant 7/151 NM_207343.4 P3Q8ND24-1
RNF214ENST00000531452.5 linkuse as main transcriptc.993G>C p.Lys331Asn missense_variant 7/151 P3Q8ND24-1
RNF214ENST00000531287.5 linkuse as main transcriptc.528G>C p.Lys176Asn missense_variant 7/152 A1Q8ND24-2
RNF214ENST00000530849.1 linkuse as main transcriptc.528G>C p.Lys176Asn missense_variant 6/135

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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 GeneticsApr 17, 2023The c.993G>C (p.K331N) alteration is located in exon 7 (coding exon 6) of the RNF214 gene. This alteration results from a G to C substitution at nucleotide position 993, causing the lysine (K) at amino acid position 331 to be replaced by an asparagine (N). 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
Pathogenic
0.95
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.067
T;.;T;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.90
D;D;.;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
0.69
N;.;N;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.16
Sift
Uncertain
0.021
D;D;D;D
Sift4G
Uncertain
0.027
D;D;D;D
Polyphen
1.0
D;.;D;.
Vest4
0.73
MutPred
0.45
Loss of ubiquitination at K331 (P = 0.003);.;Loss of ubiquitination at K331 (P = 0.003);.;
MVP
0.13
MPC
0.34
ClinPred
0.93
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117150657; API