11-117239109-C-A

Variant summary

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

The NM_207343.4(RNF214):​c.616C>A​(p.Gln206Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,604,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense, splice_region

Scores

1
8
10
Splicing: ADA: 0.2275
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
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 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.616C>A p.Gln206Lys missense_variant, splice_region_variant 3/15 ENST00000300650.9
RNF214NM_001077239.2 linkuse as main transcriptc.616C>A p.Gln206Lys missense_variant, splice_region_variant 3/15
RNF214NM_001278249.2 linkuse as main transcriptc.153+463C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.616C>A p.Gln206Lys missense_variant, splice_region_variant 3/151 NM_207343.4 P3Q8ND24-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1451950
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
721092
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:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 24, 2024The c.616C>A (p.Q206K) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a C to A substitution at nucleotide position 616, causing the glutamine (Q) at amino acid position 206 to be replaced by a lysine (K). 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
0.83
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
T;T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.78
T;.
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;L
MutationTaster
Benign
0.99
D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.079
Sift
Uncertain
0.0020
D;D
Sift4G
Benign
0.18
T;T
Polyphen
0.79
P;P
Vest4
0.71
MutPred
0.30
Gain of ubiquitination at Q206 (P = 0.0029);Gain of ubiquitination at Q206 (P = 0.0029);
MVP
0.28
MPC
0.055
ClinPred
0.62
D
GERP RS
5.0
Varity_R
0.32
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.23
dbscSNV1_RF
Benign
0.29
SpliceAI score (max)
0.030
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: rs746419775; hg19: chr11-117109825; API