Genetic Variant RNF214:p.Ile293Thr (chr11-117246867-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207343.4(RNF214):c.878T>C(p.Ile293Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,612,804 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08248907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4 link	c.878T>C	p.Ile293Thr	missense_variant	Exon 6 of 15	ENST00000300650.9	NP_997226.2	Q8ND24-1A0A024R3D4
RNF214	NM_001077239.2 link	c.878T>C	p.Ile293Thr	missense_variant	Exon 6 of 15		NP_001070707.1	Q8ND24-1A0A024R3D4
RNF214	NM_001278249.2 link	c.413T>C	p.Ile138Thr	missense_variant	Exon 6 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.878T>C	p.Ile293Thr	missense_variant	Exon 6 of 15	1	NM_207343.4	ENSP00000300650.4		Q8ND24-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000642

AC:

AN:

249128

AF XY:

0.0000592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460716

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

AC:

AN:

33432

Gnomad4 AMR exome

AF:

0.000134

AC:

AN:

44628

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26064

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39666

Gnomad4 SAS exome

AF:

0.000221

AC:

AN:

86100

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53312

Gnomad4 NFE exome

AF:

9.00e-7

AC:

AN:

1111426

Gnomad4 Remaining exome

AF:

0.0000331

AC:

AN:

60332

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:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.000131

AC:

0.000131096

AN:

0.000131096

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:

0.00

AC:

AN:

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:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000579

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.878T>C (p.I293T) alteration is located in exon 6 (coding exon 5) of the RNF214 gene. This alteration results from a T to C substitution at nucleotide position 878, causing the isoleucine (I) at amino acid position 293 to be replaced by a threonine (T). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

T;.;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;.;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.082

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.78

N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.035

D;D;D;D

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.28

B;.;B;.

Vest4

0.50

MutPred

0.29

Gain of loop (P = 0.002);.;Gain of loop (P = 0.002);.;

MVP

0.15

MPC

0.087

ClinPred

0.055

GERP RS

6.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.10

gMVP

0.21

Mutation Taster

=77/23

polymorphism

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.

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