Genetic Variant RNF214:p.Arg462Gln (chr11-117281943-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207343.4(RNF214):c.1385G>A(p.Arg462Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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]

RNF214 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21167207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 11 of 15	ENST00000300650.9	NP_997226.2	Q8ND24-1A0A024R3D4
RNF214	NM_001077239.2 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 11 of 15		NP_001070707.1	Q8ND24-1A0A024R3D4
RNF214	NM_001278249.2 link	c.920G>A	p.Arg307Gln	missense_variant	Exon 11 of 15		NP_001265178.1	Q8ND24-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 11 of 15	1	NM_207343.4	ENSP00000300650.4		Q8ND24-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000441

AC:

AN:

249374

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.000157

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000812

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.0000187

AC:

AN:

53382

Gnomad4 NFE exome

AF:

0.0000108

AC:

AN:

1111990

Gnomad4 Remaining exome

AF:

0.0000662

AC:

AN:

60394

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000241

AC:

0.0000241313

AN:

0.0000241313

Gnomad4 AMR

AF:

0.0000657

AC:

0.0000656685

AN:

0.0000656685

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000147

AC:

0.0000147072

AN:

0.0000147072

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000413

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1385G>A (p.R462Q) alteration is located in exon 11 (coding exon 10) of the RNF214 gene. This alteration results from a G to A substitution at nucleotide position 1385, causing the arginine (R) at amino acid position 462 to be replaced by a glutamine (Q). 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

0.095

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

T;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;.;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.90

L;.;L;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.030

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

1.0

D;.;D;.

Vest4

0.59

MutPred

0.21

Loss of methylation at R462 (P = 0.0746);.;Loss of methylation at R462 (P = 0.0746);.;

MVP

0.18

MPC

1.7

ClinPred

0.20

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.36

Mutation Taster

=88/12

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over