11-117239843-G-T

Variant summary

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

The NM_207343.4(RNF214):​c.661G>T​(p.Asp221Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000257 in 1,557,262 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08
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.661G>T p.Asp221Tyr missense_variant 4/15 ENST00000300650.9
RNF214NM_001077239.2 linkuse as main transcriptc.661G>T p.Asp221Tyr missense_variant 4/15
RNF214NM_001278249.2 linkuse as main transcriptc.196G>T p.Asp66Tyr missense_variant 4/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF214ENST00000300650.9 linkuse as main transcriptc.661G>T p.Asp221Tyr missense_variant 4/151 NM_207343.4 P3Q8ND24-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248766
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135060
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000445
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000263
AC:
37
AN:
1404980
Hom.:
0
Cov.:
24
AF XY:
0.0000342
AC XY:
24
AN XY:
702432
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000939
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
AF:
0.0000197
AC:
3
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000166
AC:
2

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 GeneticsMar 01, 2023The c.661G>T (p.D221Y) alteration is located in exon 4 (coding exon 3) of the RNF214 gene. This alteration results from a G to T substitution at nucleotide position 661, causing the aspartic acid (D) at amino acid position 221 to be replaced by a tyrosine (Y). 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
0.69
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;.;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.93
D;D;.;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Benign
0.90
L;.;L;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.50
N;N;N;N
REVEL
Benign
0.28
Sift
Uncertain
0.0050
D;D;D;D
Sift4G
Benign
0.099
T;T;T;T
Polyphen
1.0
D;.;D;.
Vest4
0.77
MutPred
0.23
Gain of phosphorylation at D221 (P = 0.0395);.;Gain of phosphorylation at D221 (P = 0.0395);.;
MVP
0.86
MPC
0.34
ClinPred
0.38
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
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: rs753520776; hg19: chr11-117110559; COSMIC: COSV56118059; COSMIC: COSV56118059; API